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Merkel nerve endings are found in human skin, as well as the skin of all vertebrates functioning as mechanoreceptors. Merkel cells are located in the basal layer of the epidermis both in hairy and in glabrous skin, and are often arranged in clusters. In hairy skin, Merkel cells are typically associated with large guard hairs and specialized sensory complexes known as touch domes. Merkel cells have lobulated nuclei and dense-core granules in the cytoplasm facing the associated afferent nerve terminal. Developmental studies have shown that avian Merkel cells are derived from the neural crest. In mammals, studies on transgenic mice have resulted in contradictory findings. Thus, the question of the developmental origin of mammalian Merkel cells remains to be resolved. Functionally, mammalian Merkel cell nerve endings are slowly adapting mechanoreceptors. In response to maintained mechanical stimulation they keep firing action potentials with characteristic irregular patterns. New experimental evidence strongl...

Postnatal mice lacking neurotrophin-3 (NT3) are deficient in Merkel cells of touch domes and whisker follicles. We examined the mechanism of Merkel cell loss by immunocytochemistry and electron microscopy. Merkel cell of whisker follicles of NT3 null newborns exhibited decreased immunoreactivity for cytokeratin 8 and contained apoptotic bodies that were positive for cleaved caspase-3, a marker of active apoptosis. By electron microscopy, the Merkel cells displayed aggregation of chromatin along the nuclear membrane, with the marginated chromatin forming caps at the periphery of the nucleus. Ribosomes aggregated in the cytoplasm, while dense core granules characteristic of Merkel cells were still discernible. Finally, the Merkel cells and their nuclei fragmented into apoptotic bodies. None of the apoptotic Merkel cells were contacted by nerve fibers, and their desmosomal contacts with surrounding keratinocytes disappeared. After postnatal day 6 apoptotic Merkel cells were no longer observed, and the number of surviving Merkel cells was severely reduced. They were flat and contained few osmiophilic granules. We conclude that perinatal apoptosis is responsible for the loss of Merkel cells lacking innervation in NT3 null mice.

Nude mice have a mutation in the transcription factor Foxn1 nu , resulting in downregulation of hair keratins. Although hair follicles develop normally, the hair fibers become structurally weak, curl, and break off at the surface. Nails in nude mice are deformed, based on alterations of the onychocyte differentiation process. Elemental microanalysis of the nail plate reveals marked decreases in sulfur concentrations in the nude mouse nail plates. Immunohistochemistry shows a lack of keratin 1 expression in terminally differentiating keratinocytes of the nail matrix. Instead, the typical differentiation process of the matrix is altered toward an epidermis-like differentiation pattern, comprising the production of filaggrin-containing keratohyalin granules in cells resembling those of the stratum granulosum, which are never observed in normally haired mice. The nail plate has diffuse basophilic stippling. It is thinner than normal, weak, and in most Foxn1 nu /Foxn1 nu mice breaks where it separates from the hyponychium. These studies indicate that the Foxn1 nu mutated gene has effects beyond downregulating keratin expression, including changes in filaggrin expression, and is critical for normal onycholemmal differentiation. The nails of nude mice provide new insights into the molecular controls of onychocyte differentiation, and they offer a useful model to investigate the pathogenesis of nail hypergranulosis, a common feature in human nail diseases.

Though the lining of the healthy human nose is subject of numerous investigations, age-related changes have attracted little attention. Furthermore, varying sampling sites complicate the evaluation of the available information. Reference is needed for evaluation of abnormal conditions, e.g. in persons with sleep apnea. Biopsy samples from the middle turbinate of 40 healthy humans aged 5 to 75 years were examined. Tissue samples were fixed immediately in glutaraldehyde and embedded in Epon for semi-thin sectioning and blind histological evaluation. In all age groups, patchy arrangement of different epithelial types were found. Ciliated epithelium decrease with age. Stratified and atrophic epithelial types show striking changes. Thin atrophic epithelium with conspicuously thickened basement membranes is only seen above the age of 40 years and is frequently found in older subjects. Stratified epithelial types initially increase with age, but decrease above 50 years. In the middle aged group (26 to 50 years) we found a remarkably high amount of squamous metaplasia, resulting in overall thicker epithelium becoming thinner in older subjects. In contrast, basement membranes are thinnest in the middle aged group. In conclusion, evaluating the histology of nasal respiratory epithelium must take pronounced age-related physiological changes into account.

Merkel nerve endings are mechanoreceptors in the mammalian skin. They consist of large, pale cells with lobulated nuclei forming synapse-like contacts with enlarged terminal endings of myelinated nerve fibers. They were first described by F.S. Merkel in 1875. They are found in the skin and in those parts of the mucosa derived from the ectoderm. In mammals (apart from man), the largest accumulation of Merkel nerve endings is found in whiskers. In all vertebrates, Merkel nerve endings are located in the basal layer of the epidermis, apart from birds, where they are located in the dermis. Cytoskeletal filaments consisting of cytokeratins and osmiophilic granules containing a variety of neuropeptides are found in Merkel cells. In anseriform birds, groups of cells resembling Merkel cells, with discoid nerve terminals between cells, form Grandry corpuscles. There has been controversy over the origin of Merkel cells. Results from chick/quail chimeras show that, in birds, Merkel cells are a subpopulation of cells derived from the neural crest, which thus excludes their development from the epidermis. Most recently, also in mammals, conclusive evidence for a neural crest origin of Merkel cells has been obtained. Merkel cells and nerve terminals form mechanoreceptors. Calcium ions enter Merkel cells in response to mechanical stimuli, a process which triggers the release of calcium from intracellular stores resulting in exocytosis of neurotransmitter or neuromodulator. Recent results suggest that there may be glutamatergic transmission between Merkel cell and nerve terminal, which appears to be essential for the characteristic slowly adapting response of these receptors during maintained mechanical stimuli. Thus, we are convinced that Merkel cells with associated nerve terminals function as mechanoreceptor cells. Cells in the skin with a similar appearance as Merkel cells, but without contact to nerve terminals, are probably part of a diffuse neuroendocrine system and do not function as mechanoreceptors. Probably these cells, rather than those acting as mechanoreceptors, are the origin of a highly malignant skin cancer called Merkel cell carcinoma.

Minimalinvasive Zugange verringern das Operationstrauma beim Einbringen von metallischen Implantaten zur Stabilisierung und Fixierung von Knochen. Die klinischen und anatomischen Aspekte der Zugange des Ober- und Unterarms werden aufgefuhrt, und es wird auf die moglichen Gefahren der Schadigung hingewiesen. Die Schonung nervaler und vaskularer Strukturen in Verbindung mit der moglichst kleinen Inzision und allgemeinen Gewebeschadigung spielen beim Endergebnis operativer Versorgungen im Extremitatenbereich eine entscheidende Rolle.

Das Schultergelenk ist ein muskelgesichertes Kugelgelenk mit grosten Freiheitsgraden um die 3 Korperachsen. Die flache Cavitas glenoidalis wird durch das Labrum glenoidale erganzt. Der halbkugelige Caput humeri hat eine etwa 3-mal grosere Flache als die Pfanne mit dem Labrum. Die Gelenkkapsel erstreckt sich zwischen dem Rand der Pfanne und dem Collum anatomicum des Humerus. Sie ist schlaff und umschliest das Labrum und die Sehne des Caput longum des M. biceps brachii. Sie wird ventral durch die Ligg. glenohumeralia und das Lig. coracohumerale verstarkt. Die obere, vordere und dorsale Verstarkung der Kapsel erfolgt durch die Sehnen der Muskeln der Rotatorenmanschette. Nach distal bildet die Kapsel den Recessus axillaris. Die sensible Innervation der Gelenkkapsel erfolgt uber die Aste des ¶N. axillaris und dorsal z. T. uber die Aste des N. suprascapularis. Die uberwiegende Anzahl sensibler Nervenendigungen besteht aus Schmerzrezeptoren. Die Anzahl der Mechanorezeptoren ist gering. Dementsprechend ¶erfolgt die Wahrnehmung der Stellung des Gelenks durch die Propriorezeptoren der Schultergelenkmuskulatur. Die Gefase begleiten die Nervenaste und stammen aus den Aa. circumflexa humeri anterior und posterior und aus der A. suprascapularis.

The lectin binding pattern of muscular microvessels in chick, quail and chick/quail chimeras was analysed. Paraffin wax sections of muscles from embryonic and adult animals were used. The biotin-labelled lectins were detected by avidin-alkaline phosphatase complex. The following lectins bound to muscular microvessels including arterioles, capillaries and venules of both species: SNA-I (Sambucus nigra agglutinin), MAA (Maackia amurensis agglutinin), AIA (Artocarpus integrifolia agglutinin), VAA-I, VAA-II and VAA- III (Viscum album agglutinin I–III), WGA (wheat germ agglutinin), LEA (Lycopersicon esculentum agglutinin). Endomysium and basement membranes of muscle fibres were also stained to a variable extent and intensity. Only SNA-I stained almost exclusively the endothelium of blood vessels. WFA (Wisteria floribunda agglutinin) bound to the quail endothelium only. MPA (Maclura pomifera agglutinin) marked vessels in adult muscles of chick and quail, but embryonic vessels were stained in quail only. Our results show that lectin histochemistry is a useful tool for visualisation of microvasculature in avian species. In particular, WFA and MPA can be used to determine the origin of endothelia in chick/quail chimeras.

Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistochemistry indicate a low degree of differentiation and high malignity of the tumors, which is consistent with the clinical behavior of Merkel cell carcinomas.

We studied carbohydrate residues of glycoproteins and proteoglycans (PGs) in peritoneal Pacinian corpuscles of five adult cats. Terminal monosaccharides of glycoproteins and related polysaccharides were identified by lectin histochemistry and the PGs and glycosaminoglycans (GAGs) by specific antibodies. The most intensive lectin staining reactions indicated an abundance of glycoconjugates with terminal mannose (Man) or sialic acid residues, but no complex-type oligosaccharides were detected within the corpuscles. Terminal fucose (Fuc) and galactose (Gal) residues typical for O-linked mucin-type glycoproteins generally associated with high water binding capacity were also absent. Antibodies against unsulfated chondroitin (C-0-S), chondroitin-4-sulfate (C-4-S), and decorin showed positive reactions in the interfibrillar spaces between the lamellae, around collagen fibers, and around the lamellae of the perineural capsule, especially in the outer parts known to contain Type II collagen. Biglycan showed a preference for the innermost part of the perineural capsule (intermediate layer), known to contain Type V collagen. Collagen V and biglycan are both linked to growth processes. Hyaluronic acid (HA), chondroitin-6-sulfate (C-6-S) chains, and a chondroitin sulfate proteoglycan (CSPG) were colocalized in the terminal glia. The study of carbohydrates with high water binding capacity may contribute to our understanding of the high viscoelasticity of Pacinian corpuscles.

We have investigated the developmental origin and ultrastructure of avian Merkel cells by electron microscopy and chick/quail transplantation experiments. On embryonic day 3, chick leg primordia were homotopically grafted onto Japanese quail host embryo. Fourteen days later, quail cells that had migrated into grafted chick legs were identified according to the masses of heterochromatin associated with the nucleolus that are characteristic for quail. Both in chick and quail, Merkel cells are usually located in the dermis just below the epidermis. They are placed between nerve terminals either individually or in small groups wrapped in sheaths that are formed by glial cell processes. Occasionally, some Merkel cells appear in nerve fascicles and within Herbst corpuscles. Merkel cells, as well as glial cells, in grafted chicken legs were of quail origin. This finding provides evidence against the epidermal origin of avian Merkel cells and indicates that Merkel cells are derived from neural crest cells that colonise, together with glial cells and melanocytes, the developing limb primordium.

The sensory innervation of the hard palate of the rhesus monkey was studied by light and electron microscopy. The mucosa of the hard palate is subject to a particularly heavy mechanical load requiring functional specialisation of the horny epithelium in the form of thickenings - the papilla incisiva and eight pairs of rugae palatinae. A thin layer of firm connective tissue (lamina propria) attaches the mucosa to the periost of the hard palate. Sensory nerve fibres were found most abundantly in the papilla incisiva and first rugae palatinae. Their number decreases in an aboral direction. Five types of sensory nerve endings were found. Free nerve endings were ubiquitous in the epithelium and lamina propria. Merkel nerve endings were found in the basal layer of the epithelium of the papilla incisiva and rugae palatinae. Meissner corpuscles were located in the connective tissue between epithelial pegs, while lamellated corpuscles were seen below the epithelial pegs. Ruffini corpuscles were found in the deeper layer of the lamina propria. Thus, a variety of sensory nerve endings were found in the hard palate, especially in those areas that are in close contact with the tongue during chewing of food. This rich innervation suggests an important role in monitoring the mechanical properties of food and the position of the tongue.

Summary In order to investigate the sensory innervation, the upper cervical spine of a small laboratory marsupial (monodelphis domestica) was examined with serial section light microscopy and re-embedding of selected sections for electron microscopy. Large numbers of free nerve endings supplied by Aδ- and C-fibres were found in the longitudinal ligaments and facet joint capsules. Electron microscopically, areas of direct contact between axon and collagen fibres of the surrounding connective tissue separated only by the basal lamina were observed. Such structural adaptations suggest mechanoreceptive or polymodal nociceptive functions. In addition, about 100 small lamellated corpuscles were found in the longitudinal ligaments mainly concentrated around the first intervertebral disk. Electron microscopy shows finger-like processes extending from the axon terminal into the inner core lamellae. These are the likely sites of the mechanoelectric transduction process. Smaller numbers of lamellated corpuscles were seen in the lower intervertebral disks and facet joint capsules. Lamellated corpuscles are known to function as rapidly adapting mechanoreceptors supplementing information supplied by muscle spindles to the CNS about position and movement of the cervical spine.

Our experiments addressed the problem of the regulation of the number of mechanoreceptors by sensory axons and/or their peripheral target tissues. According to a previous study (Zelená et al. 1997) white leghorn chickens have more muscle spindles in the plantaris muscle (45.4+/-7.8; mean+/-SD) than the Japanese quail (35.3+/-4.8) and significantly more Herbst corpuscles in the crural region (380.0+/-85.0) than the quail (124.9+/-32.8). Embryonic chick-quail chimeras were therefore used as a model with distinct recombinations of the nerve supply and peripheral tissue for studying the developmental control of these mechanoreceptors. The chick host leg bud was replaced with a quail leg bud of equal age and vice versa on embryonic day 3, prior to the onset of innervation of the periphery. Shortly before hatching the chimeras were sacrificed and muscle spindles and Herbst corpuscles counted. Recombinations of chicken nerves with quail limb buds have shown that the richer nerve supply by chick Ia axons induced a significant increase in the number of muscle spindles in the plantaris muscles (55.5+/-13.4) of the grafted quail limb. In some instances, a similar increase in spindle numbers was also found in control legs grafted onto hosts of the same species. In the reverse type of chimera where chick embryo legs were grafted onto quail hosts, spindles developed in lower numbers (27.3+/-3.2). In that case the lower number of Ia axons in quail nerves induced a lower number of spindles in the chicken muscle. The numbers of Herbst corpuscles were, however, low in both types of chimera. Quail legs grafted onto host chick embryos contained 126.8+/-26.4 corpuscles, presumably due to a restrictive influence of the smaller crural area in the quail. Chick legs grafted onto quail hosts had only 99.6+/-34.1 crural corpuscles; the target area in chick embryo legs failed to attract more quail axons and/or to induce axonal sprouting. The developmental regulation of the number of the two types of mechanoreceptors examined in our study thus differ. While sensory axons appear to play the dominant role in the development of muscle spindles, their role seems to be restricted by hitherto unknown peripheral factors during the development of Herbst corpuscles.

The aim of the present study was to describe the types and location of sensory nerve endings in the glans penis of the rat on the basis of light and electron microscopy. Free nerve endings are abundant throughout the glans and are derived from either thinly myelinated A delta or unmyelinated C fibers. The free nerve endings derived from A delta fibers often extend into the epidermis as far as the granular layer and exhibit buttonlike terminal thickenings. The distal urethra contains many free nerve endings from C fibers. Numerous lamellated corpuscles are present. Each corpuscle, innervated by one or two medium diameter myelinated nerve fibers, consists of 4-10 spiralling and intertwined inner cores enveloped by Schwann cell lamellae. The corpuscles are usually enclosed by a perineural capsule, although some located near the epidermis lack a capsule. Lamellated corpuscles in the superficial dermis are located adjacent to but not directly under a penile spine and change their orientation when the glans is erect. The dermal papillae of the penile spines are devoid of any neural structure. Lamellated corpuscles are also located within the trabeculae of the corpus spongiosum glands and in the lamina propria of the urethra. Occasionally, unmyelinated nerve bundles are seen inside these corpuscles. Ruffini corpuscles are few in number and are located in the deep connective tissue near the os penis. They have an incomplete connective tissue capsule and the nerve terminals are anchored between collagen fiber bundles. No Merkel nerve endings, Meissner, or Vater-Pacini corpuscles were found in any of the sections. We conclude that the glans penis of the rat contains a sensory receptor complement that is generally similar to the human glans penis but is unlike the glabrous and hairy skin.

The human hand is a complex organ serving the functions of grip and touch. The mechanoreceptors of the hand can be categorised into those located within skin and subcutaneous tissues and those associated with joints and muscles providing the central nervous system with information about position of movement of hand and fingers. In addition to mechanoreceptors there are numerous free nerve endings reacting to thermal and/or painful stimuli generally referred to as polymodal nociceptors. They are found in the connective tissue of the locomotion apparatus as well as the skin and even enter the epidermis. Morphologically these are terminal branches of afferent nerve fibres without any specific structures around these ‘free’ nerve endings in marked contrast to the different types of mechanoreceptors.

Stability of the shoulder joint emanates from numerous mechanisms including articular geometry, static restraints (capsuloligamentous tissue), dynamic (muscular) stabilizers, and intra-articular forces. Capsuloligamentous structures not only provide mechanical restraint to joint subluxation, but also provide vital sensory feedback information that regulates involuntary muscular activation for joint stability (neuromuscular control).

The sensory innervation of the anal canal of the pig was investigated by light and electron microscopy. The distribution of the different types of sensory nerve endings correlates with the histology of different zones: (1) After the rectal mucosa there was a zone lined with nonkeratinized stratified squamous epithelium. (2) A middle zone was lined with keratinized stratified squamous epithelium. Here the dermis already showed a papillary and a reticular layer. (3) The last zone showed hairy skin with a high hair density. The following nerve endings were found: Free nerve endings reached the stratum superficiale in nonkeratinized squamous epithelium and the stratum granulosum in the keratinized squamous epithelium. Dermal free nerve endings were found in all zones near the epithelium and two different types were identified as those derived from C-fibers and those from A-delta-fibers. Merkel nerve endings showed different features depending on their location. Few Merkel-like cells were found in the epithelium of the anal crypts. Typical Merkel ‘Tastscheiben” were located at the base of epithelial ridges or pegs in zones 2 and 3. The number of Merkel cells varied up to 200. The myelinated afferent fiber supplied 10–15 Merkel cells. Merkel cells were also found regularly in the outermost layer of the external rooth sheath of hair follicles at about the same level as perifollicular nerve endings. Lamellated corpuscles were found in the dermis of all zones except the cranial part of zone 1, where the anal crypts are located. Generally they consisted of a central nerve terminal which may be branched. Each terminal was surrounded by an inner core of concentrically arranged lamellae of the terminal Schwann cell and one or several inner cores were included in a capsule of perineural cells. The size of the corpuscle, the regularity of the inner core and the number of capsular layers depended on the location of the corpuscle. The closer it was to the epithelium, the less well developed was the capsule and the smaller the corpuscle tended to be. Perifollicular nerve endings andpilo-Ruffinicomplex are unique features of the sensory innervation of hairy skin. They were regularly found with the large guard hairs.

The three-dimensional morphology of the innervation of touch domes in the hairy skin folds of cat forepaws was investigated by the confocal laser scanning microscopic analyses of sections stained immunocytochemically with primary antibodies for protein gene product 9.5, neurofilament 200 and cytokeratin 20 in combination with transmission electron microscopic observations. One square centimeter of interdigital skin can contain as many as 68 touch domes. Each touch dome can have up to 150 Merkel cells and all are innervated by a single large-caliber afferent myelinated nerve fiber at the level of the palisade endings around the guard hair. It gives rise to multiple long, myelinated branches. Each final myelinated branch gives rise to several short and fine unmyelinated branches, supplying approximately 15 Merkel cell-axon complexes. Each Merkel cell is typically contacted by multiple small discoid endings instead of by a large single one. Discoid endings on separate Merkel cells were usually the distal ends of the unmyelinated branches, although, some were en-passant swellings of the branches. Only a few Merkel cell-axon complexes at the marginal zone of each territory could also be supplied by adjacent final myelinated branches. Each Merkel cell is surrounded by protrusions of keratinocytes that are penetrated by several collagen bundles of the dermis. This intricate pattern of innervation may explain the unique irregular discharges of action potentials typical for this type of mechanoreceptor.

The skin is the largest sensory organ in mammals, containing huge numbers of free nerve endings serving as polymodal nociceptors as well as specific corpuscular mechanoreceptors i.e.Meissner, Ruffi...

OSAS-patients complain about nasal disorders. Irritation of the nasal mucosa often leads to termination of nCPAP treatment. The aim of this study is to evaluate whether symptoms are related to histologic changes of the nasal mucosa of the head of the middle turbinate in OSAS-patients. Semi-thin sections of epon-embedded middle turbinate biopsy samples from 35 male patients (age 51-75 yr) with OSAS were compared with those of 10 healthy men (age 51-75 yr). In untreated OSAS-patients atrophic epithelium is common whereas ciliated epithelial types are rare. After short-time nCPAP therapy (mean 581h) patches of ciliated epithelium and squamous metaplasia reappear. Short-term nCPAP leads to a partially restoration of the mucosal architecture. During long-time nCPAP therapy (mean 6.737h) squamous metaplasia with conspicuous intraepithelial connective tissue papillae predominates whereas pseudostratified ciliated epithelium is missing. Dense round cell infiltrates in the lamina propria are frequently found. Rhinitic symptoms in OSAS-patients are correlated with marked histological changes of the respiratory epithelium of the head of the middle turbinate. Histological changes in untreated OSAS differ from those of patients during nCPAP-treatment.

This study focused on those types of mammalian nerve endings originally described by Merkel in 1875. In all mammals, Merkel cells are found in the basal layer of the epithelium usually in close contact with nerve terminals. The Merkel cell is always positioned between the direction of the mechanical stimulus and the nerve terminal. Any similar cell without nerve contact may have neuroendocrine, but not mechanoreceptor functions. Thus, such cells should not be called Merkel cells, as there is no evidence for any relationship with those structures originally described by Merkel.

Whiskers are highly sensitive touch organs in all mammals apart from man. A blood sinus encloses the hair follicles completely or almost completely. One sinus hair has several thousand sensory nerve endings. Most of them are located in the epithelial thickening below the sebaceous gland. A large number of Merkel cells with associated nerve endings can be found in that region. The absolute number depends on the species and size of the hair. In cat and rat, large whiskers can have up to 2000 Merkel cell-nerve endings innervated by approximately 100 myelinated axons.

Glycoproteins and proteoglycans are involved in tumor genesis, progression, and metastatic activity.

Chick/quail chimeras and double transgenic Wntl -cre/R26R mice, in which neural crest cells are permanently marked by expression of s-galactosidase, are evidence that Merkel cells in Merkel nerve endings of birds and mammals are neural crest derivatives. Like melanoblasts their precursors colonise the skin. Cytokeratin 8- and 18-positive Merkel cells in mouse whisker follicles are postmitotic cells. They are Ki 67-negative and their nuclei exhibit features of differentiated resting cells. In contrast, Merkel cell progenitors are likely to be proliferating cells. Simple cytokeratins are not suitable markers for their identification. Possible progenitors of Merkel cells that contain dense core granules can be identified using electron microscopy in the connective tissue surrounding the bulge region of the whisker follicle. Possible progenitors of Merkel cells in epidermis are s-galactosidase-positive, but cytokeratin-negative. Verification of the Merkel cell precursor nature of these cells requires specific markers that will enable us to distinguish them from precursors of melanoblasts. Thus, the question of the location of proliferative Merkel cell progenitors remains open.

Summary The topography of muscle spindles and Golgi tendon organs in the rotator cuff and surrounding shoulder muscles of a small laboratory marsupial ( monodelphis domestica ) were studied using light microscopy of serial sections. The shoulder joint of monodelphis has a large degree of freedom of movement allowing this animal to use the upper extremities for a wide range of activities like climbing and manipulating food. Thus, similar to the situation in man the shoulder joint is mainly secured by muscles. Silver stained serial paraffin sections were examined under the light microscope and the distribution of muscle spindles and Golgi tendon organs was reconstructed using three-dimensional image processing. In the two animals examined 113 and 131 muscle spindles respectively were found within the 4 rotator cuff muscles. In addition, 76 and 40 Golgi tendon organs respectively were seen at the musculo-tendinous junctions of these muscles preferentially close to the insertion at the humerus head. Also the surrounding shoulder muscles contain both muscle spindles and Golgi tendon organs in large numbers, but the ratio of Golgi tendon organs per muscle spindle appears to be lower. Number and localization of muscle spindles and Golgi tendon organs suggest, that these receptors are important for both reflex control of shoulder muscle tone as well as monitoring of static position and movement in the shoulder joint.

The topography and structure of corpuscular mechanoreceptors in the shoulder joint capsule and periarticular connective tissue of a small laboratory marsupial (monodelphis domestica) were studied using light and electron microscopy. This animal is known to use its upper extremities for a wide range of activities like climbing and manipulating food. Thus, the shoulder joint of this animal species has a similar wide range of movement as the human shoulder joint, but is small enough for serial sectioning in its entirety. Silver stained serial paraffin sections were examined under the light microscope and the distribution of the different types of mechanoreceptors was reconstructed using three-dimensional image processing. In addition, selected mechanoreceptors were studied electron microscopically. Approximately 100 small lamellated corpuscles were found in the dense connective tissue of the joint capsule close to the insertion on the scapula and in the thickening of the joint capsule close to the glenoid labrum. Ruffini corpuscles were found in much smaller numbers in the moderately dense connective tissue of the axillary region. Only very few Vater-Pacinian corpuscles were seen in the soft periarticular connective tissue. The large number and localization of mechanoreceptor corpuscles in the shoulder joint capsule especially close to the glenoid labrum suggests, that these specialized nerve endings are likely to play an important role in control of joint movement. They can induce protective reflexes during extreme movements in the shoulder joint preventing shoulder luxation by increasing the tone of muscles pressing the humerus head into the glenoid cavity.

The sensory innervation of the papilla incisiva in the hard palate of the domestic goat was studied with light and electron microscopy, supplemented by electrophysiological studies of free nerve endings. The goat lacks incisor teeth. Grass and leaves are not bitten, but pulled off by pressing them between the tongue and papilla incisiva. Thus, the masticatory mucosa is subject to particularly heavy mechanical loads requiring functional specialization of the horny epithelium in the form of thickening, i.e., the papilla incisiva and 12-14 pairs of rugae palatinae. A thin layer of firm connective tissue (lamina propria) attaches the mucosa to the periost of the hard palate. Sensory nerve fibers were found most abundantly in the papilla incisiva. Their number decreased drastically in aboral direction. A section through the first four rugae palatinae contains only about 10% of the number of free nerve endings found in the same area of mucosa from the papilla incisiva. Four types of sensory nerve endings were found. Free nerve endings were seen ubiquitously in the epithelium and superficial layer of the lamina propria. Merkel nerve endings were found in the bases of the epithelial thickenings in the papilla incisiva and rugae palatinae. Few Ruffini corpuscles were found in the deeper layer of the lamina propria, while lamellated corpuscles were seen just below the basement membrane of the epithelial pegs. Thus, a variety of sensory nerve endings were found in the hard palate, especially in those areas that are in close contact with the tongue during chewing of food. This rich innervation suggests an important role in monitoring the mechanical properties of food. Recordings were made from cell bodies supplying these terminals. Classic low-threshold, slowly adapting responses were observed in Ass afferent populations. This activity was probably mediated by Merkel type endings. Alternately, high-threshold and suprathreshold responses obtained from Adelta category afferents were likely to be nociceptive. In support of this, threshold and suprathreshold sensitization was observed following injection of serotonin into the receptive field of Adelta populations. This activity was likely to be derived from the aforementioned free nerve endings.

BACKGROUND We investigated the pattern of distribution of corpuscular sensory nerve endings in the shoulder region of the laboratory mouse in relation to their functional properties. METHODS Twelve adult female white NMRI-F2-mice were used. The topography of sensory nerve endings in the shoulder joint region was reconstructed by three-dimensional image processing by using serial silver-stained sections of paraffin-embedded samples. Semithin sections obtained from additional samples were used for light microscopy. RESULTS Within the fibrous layer of the joint capsule, three types of mechanoreceptors were identified: small lamellated corpuscles of the Pacini type, Ruffini corpuscles, and Golgi tendon organs. Intracapsular small lamellated corpuscles of the Pacini type (in an average number of 29/joint) were found mainly in three areas: in the predominantly flaccid tissue of the axillary region, in the denser ventromedial parts of the capsule, close to the scapula, and in the tight texture of the fiber bundles near the glenoid labrum. Ruffini corpuscles were identified only in small numbers (2/joint) in the ventral aspect of the articular capsule of two animals. Golgi tendon organs (14 or 15 receptors/joint) were discovered predominantly in close vicinity to the joint capsule at the muscle tendon junction of the inserting rotator cuff muscles and in the biceps brachii and triceps brachii muscles. CONCLUSIONS In view of their location in the shoulder joint capsule and the glenoid labrum, corpuscular mechanoreceptors evidently play an important role in joint control by inducing protective reflex actions in phases of extreme or abnormal movement. The density of sensory receptors in distinct areas of the shoulder joint capsule appears to be related to zones that are subjected to increased biomechanical stress during physical activity.

The ultrastructure and distribution patterns of sensory nerve endings in the dorsal knee joint capsules of the beagle dog (Canis familiaris) have been investigated using light and electron microscopy. Each dorsal knee joint capsule was divided into four quadrants, cut into small pieces and then processed for electron microscopy. Free nerve endings and corpuscular nerve endings (Ruffini and lamellated corpuscles) were found. They were most frequently observed in the medial-proximal quadrant of the dorsal joint capsule. All nerve endings were found to be situated within or adjacent to the fibrous layer of the capsule. No nerve endings were found within the synovial layer. Free nerve endings were usually situated at the border between the fibrous layer and the synovial layer near blood vessels. Their associated afferent axon was myelinated (1.5-2.5 microns in diameter) or non-myelinated (0.3-1.5 microns in diameter). Ruffini corpuscles were found in the fibrous layer and within the dorsal ligamentous apparatus. Each Ruffini corpuscle was surrounded by a multilayered perineural capsule which was usually incompletely developed. The perineural capsule is the continuation of the perineurium of the afferent axon and gives a cylindrical form to the corpuscles. Ruffini corpuscles were present as single, cylindrical structures (small corpuscles) or as aggregates of these cylinders (large corpuscles). Both varieties consist of terminal nerve endings surrounded by collagen fibres which pass through the opened ends of the cylinders. The diameter and length of the small Ruffini corpuscles were 80 microns and 400 microns, as compared to 200 microns and 800 microns for the large aggregated forms. The supplying afferent axons of both types were 4-5 microns in diameter. Two types of small lamellated corpuscles could be observed in the fibrous layer: very small corpuscles, 55 microns long, 25 microns wide and medium corpuscles, 100 microns long, 40 microns wide. Each consists of an inner core of terminal Schwann cells, a nerve terminal and a perineural capsule. Some lamellated corpuscles had two inner cores and two nerve terminals. The diameter of the afferent axon was approximately 6 microns. Vater-Pacini corpuscles were not found in the dorsal knee joint capsule of the dog.

The function of Merkel cells in mechanotransduction has remained controversial Single unit recordings were made from Merkel cell receptors (sinus hair type I, St I) and another slowly adapting mechanoreceptor (sinus hair type II, St II) in isolated rat sinus hairs by applying controlled mechanical displacements to the hair shaft. Chloroquine (50-300 microM) caused a concentration dependent inhibition of Merkel cell receptor responses to mechanical stimulation. In contrast, both stimulated and spontaneous spike activity of St II receptors was increased by the same concentrations of chloroquine. Ultrastructural examination of chloroquine treated sinus hairs revealed swollen Merkel cells with multiple vacuoles and randomly distributed granules while other neural and surrounding structures showed no striking morphological changes. These results suggest that the Merkel cell plays a mechanotransducer role in Merkel cell receptors.

Experiments were performed on slowly adapting type I mechanoreceptors in an isolated rat skin-nerve preparation (SA I receptors) and in an isolated rat sinus hair preparation (St I receptors). Merkel cells were stained in vitro with the fluorescent dye quinacrine and irradiated with ultraviolet (UV) light (2 mW for up to 1 h) while recording receptor responses to standard mechanical stimuli every 30 s. In addition, thresholds for electrically evoked action potentials were tested by applying electrical stimuli to the skin through the same stylus used for mechanical stimulation. UV irradiation resulted in abrupt failure to respond to mechanical stimuli in 73% of the SA I receptors examined (n = 37) within less than 1 h. This confirms previous reports of phototoxic destruction of Merkel cells. However, several minutes after the receptors failed to respond to mechanical stimulation, thresholds for electrical stimuli applied to the receptive field increased sharply. About 40% of the St I receptors (n = 13) irradiated with UV light following quinacrine staining stopped responding to bending of the hair within 1 h. In contrast, none of the seven St II receptors treated in the same way showed significant changes in the responses. Electron microscopic examination of sinus hairs after quinacrine staining alone showed slight changes in the appearance of Merkel cells, and in particular enlargement of the perinuclear space. These changes did not affect receptor responses. Electron microscopic studies of sinus hairs with receptors that had maintained normal responses to mechanical stimuli after quinacrine staining and 1 h of UV irradiation revealed that a substantial number of Merkel cells still had a normal ultrastructure while adjacent nerve terminals were severely swollen and partially compressing the Merkel cells. No changes were observed in lanceolate nerve terminals forming the morphological substrate of St II receptors. These results demonstrate that sensitivity to phototoxic destruction following quinacrine staining varies greatly among Merkel cells, with some maintaining normal function and ultrastructural appearance even after 1 h of UV irradiation. On the other hand there is clear evidence that the phototoxic damage affects the nerve terminals as well. Such experiments can therefore not provide conclusive proof about the role of Merkel cells in these mechanoreceptors.

Sinus hairs were isolated from rats and examined in an isolated organ bath while superfused with oxygenated synthetic interstitial fluid. The distal end of the deep vibrissal nerve was teased for single unit recordings of responses from slowly adapting mechanoreceptors to standard bending of the hair. Sinus hair type I and type II receptors could be clearly identified by their respective characteristic firing pattern. Their responses were stable for at least 5 h even if the sinus hair had been stored at 4 degrees C for 24 h beforehand. Electron microscopic examination of these hairs at the end of experiments showed well preserved ultrastructure without abnormalities. The short diffusion distances in this preparation make it well suited for studying drug effects with the aim of investigating the mechanoelectric transduction process in these receptors.

During the course of a study on the morphology of periodontal ligament mechanoreceptors it was observed that a direct relation, without intervening bone, existed between the mandibular canine and first premolar tooth roots in the cat. An area, representing a window in the alveolar septal bone, extended 2–3 mm from the apex towards the tooth crown. Ruffini nerve terminals were observed amongst the collagen bundles in the ligament between the roots of the two teeth. Light and electron microscopy were used to identify the receptors. It is proposed that a periodontal ligament mechanoreceptor can respond to forces applied to adjacent teeth; movement of both teeth need not occur. This may explain the observation made in the past that single periodontal ligament mechanoreceptors respond to forces applied to more than one tooth.

A correlative morphological study was carried out on two electrophysiologically identified and located periodontal ligament mechanoreceptors in anaesthetised cats. One mechanoreceptor had its cell body in the mesencephalic nucleus and the other had its cell body in the trigeminal ganglion. Physiological recordings were made from each of their cell bodies. The two receptors were located by punctate and electrical stimuli in the labial aspect of the periodontal ligament of the left mandibular canine tooth. Both receptors had similar positions relative to the tooth apex and fulcrum and were situated in the labial part of the ligament in each tooth. The receptor loci were marked, and these regions were studied in a series of semi-thin and ultra-thin sections. Only Ruffini nerve endings were observed under each ink mark. Both Ruffini nerve endings branched, were unencapsulated and were incompletely surrounded by terminal Schwann cells with extensions projecting towards collagen bundles. The results indicate that periodontal ligament mechanoreceptors with cell bodies in the mesencephalic nucleus and those with their cell bodies in the trigeminal ganglion can both be Ruffini nerve endings. Furthermore, there was no apparent morphological difference between the two periodontal ligament mechanoreceptors.

This study is concerned with the distribution and ultrastructure of sensory nerve endings in the beak skin of adult Japanese quail (Coturnix coturnix japonica). The following nerve endings were found: free nerve endings, clusters of dermal Merkel nerve endings, Herbst corpuscles and Ruffini corpuscles. The latter were found only in the dermis of the tip of the upper beak. The remaining endings were present in the skin of all areas of upper and lower beak. Free nerve endings were supplied by either thin myelinated axons or unmyelinated C-fibers and were localized in the dermis close to the basal layer of the epidermis. Merkel cells formed clusters (up to 50) localized below and between the epidermal cones of the beak skin. Disc-shaped thickenings of nerve endings were squeezed between individual Merkel cells. Small Herbst corpuscles were found in the dermis close to the epidermal cones of the beak skin. Large Herbst corpuscles occurred in deep layers of the dermis. The Ruffini corpuscles were cylindrical in shape (80 microns x 400 microns) and arranged in groups of up to ten corpuscles. Each corpuscle was surrounded by an incomplete fibrous capsule.

The topogenesis of the hindlimb nerves of Splotch homozygous mutant mouse embryos was studied using light and electron microscopy. Homozygous mutants show multiple defects of neural crest-derived tissues. The defects increase along a rostro-caudal gradient. The cervical and upper thoracic segments have small spinal ganglia, and Schwann cells are associated with the spinal nerves. In the lumbo-sacral region neurulation is not complete, and the derivatives of the neural crest are missing. The lumbo-sacral nerve trunks are formed by ventral roots only. They are occasionally associated with presumptive glial cells that have migrated from the spinal cord for a short distance. Beyond the vertebral primordia, the spinal nerves are not accompanied by Schwann cells. No compartmentalization of the axons within the lumbo-sacral nerves was visible, where as Schwann cells did segment the nerve into the fascicles in brachial nerves. The lumbo-sacral plexus develops, and its branches grow into the hindlimb despite the absence of Schwann cells. On day 13.5 of gestation, the lumbo-sacral nerve trunks extend well into the distal calf. They are topographically correctly positioned. Their branches enter the muscle primordia and form contacts with their mesenchymal cells though the cutaneous branches are missing. Generally, the outgrowth of lumbo-sacral nerves is slower than in phenotypically normal littermates, whose nerves reach the foot plate at corresponding stages of development. These results demonstrate that the lumbo-sacral plexus and the topographically correct position of lumbo-sacral nerve trunks develop despite the absence of Schwann cells. Therefore Schwann cells are not necessary for the outgrowth and guidance of axons within the limb.

The origin of cells covering the nervous system and the cutaneous receptors was studied using the quail-chick marking technique and light and electron microscopy. In the first experimental series the brachial neural tube of the quail was grafted in place of a corresponding neural tube segment of the chick embryo at HH-stages 10 to 14. In the second series the leg bud of quail embryos at HH-stages 18-20 was grafted in place of the leg bud of the chick embryos of the same stages and vice versa. It was found that all meningeal layers of the spinal cord, the perineurium and the endoneurium of peripheral nerves, as well as the capsular and inner space cells of Herbst sensory corpuscles, develop from the local mesenchymal cells. Schwann cells and cells of the inner core of sensory corpuscles are of neural crest origin. The precursors of Merkel cells migrate similarly to the Schwann cells into the limb bud where they later differentiate. This means that in addition to the Schwann cells and the melanocytes a further neural crest-derived subpopulation of cells enters the limb.

The sense of touch developed early in phylogeny. One of the reasons might be that this sense is highly essential for survival: using this sense, the newborn animal explores its new surroundings, and by doing this, it might come across sources of food and support. For this purpose the skin contains complex nervous structures, named “touch organs” or “mechanoreceptive complexes” (Halata, 1975). These organs develop at different stages before birth depending on their significance for the animal., In animals which leave their parents at an early point they are fully developed immediately after birth (Walter, 1960/61), whereas with those animals which stay with their parents for a longer period of time, the process of maturation takes longer.

Ultrastructural studies of sensory endings in monkey posterior medial knee joint capsule were undertaken. Three distinct sensory nerve endings have been identified: free nerve endings, Ruffini corpuscles, and Pacinian corpuscles. The free nerve endings are present in all layers of the joint capsule excluding the synovium. Two types of Ruffini corpuscles have been found in the fibrous layer. The first type is characterized by a thin perineurial capsule, the second type by a thicker perineurial capsule and extensive intra-capsular space. Both types of Ruffini corpuscles are innervated by approximately one to four myelinated axons which lose their sheaths as they course through the corpuscle. They terminate on collagen fiber bundles as distinct swellings with spiny membrane projections that are covered by a thin basal lamina. These terminals contain abundant mitochondria, agranular vesicles, and irregularly arranged neurofilaments and neurotubules. Two types of Pacinian corpuscles were occasionally observed. The first was a small, typically laminated structure with an inner core at the layer between the synovium and the fibrous layer and between the fibrous layer and muscle/ligament; larger Vater-Pacinian corpuscles were noted only at the boundary between the fibrous layer and the muscle/ligament layer.

The present study documents the characteristics of innervation of the rhinarium or hairless rat snout skin by light and electron microscopy. The outer glabrous surface is covered with a stratified squamous epithelium that forms both rete pegs and rete ridges, the latter on the inferior border near the philtrum. The glabrous skin contains numerous presumptive epidermal and dermal free nerve endings (FNE's), Merkel terminals at the base of the rete ridges and pegs, and simple, nonencapsulated corpuscles. A second region of dense innervation, found on an elevation of the inner wall of the vestibule, contains similar components of innervation, with the exception that no Merkel terminals were identified. Since no Merkel terminals were present in this area of the vestibule, intraepidermal as well as dermal FNE's could be identified with certainty. This skin is covered by a thin squamous epithelium overlying dense connective tissue. The simple corpuscles are similar to those in the rhinarium, as well as resembling those described in other species. FNE's were frequently observed intimately associated with simple corpuscles. Several examples of large FNE's with two to three layers of cytoplasmic lamellae were found, suggestive of transitional forms between FNE's and simple corpuscles. Thus, the pattern of sensory innervation in the glabrous rat snout skin is similar to that found in other furred species described to date, but in addition, the sensory innervation of ridged skin in the rat also resembles that of epidermis organized into rete pegs. This dense sensory innervation may be correlated with whisking behavior of the predominantly nocturnal rat.

Touch organs of the skin in mammals consist of a mechanical transducting component and a sensory component. In the hairy skin, examples of these mechanical transducting components can be seen in the epithelium of hair follicles, and in the hairless skin in the epidermal papillae of the cone skin or the epidermal ridges of the ridges skin. In hairy skin all sinus and guards hairs and most of the vellus hairs are touch organs. The sinus and guard hairs are equiped with Merkel endings, free nerve endings, palisades of lanceolate nerve endings and pilo-Ruffini complexes. The total number of nerve endings varies in guard hairs between 50-200 and between 500-2000 in sinus hairs depending on the size of the follicle. The skin surrounding the body orifices, glabrous skin of the tip of the nose and skin of the finger tips is rich in touch organs. Touch organs of the cone skin known as Eimer organs consist of free nerve endings and of Merkel endings innervating the epidermal cone. Below these cones, the papillary layer shows small lamellated corpuscles and also free nerve endings. In the ridge skin epithelial ridges and crypts, the corresponding dermal papillae, their blood vessels and nervous elements together form the touch organs. In the basal layer of the glandular ridge up to 10 Merkel nerve endings are visible. In young individuals the connective tissue papilla of each crypt shows one Meissner corpuscle and several free nerve endings.

The sensory innervation of primate sinus hairs has been studied by light and electron microscopy. For light microscopy paraffin sections as well as thick frozen sections were impregnated with silver and compared with serial semi-thin sections of tissue prepared for electron microscopy. One type of sensory terminal is present in the epidermis surrounding the hair follicle, and four specific nerve terminals have been identified within the blood sinus. An epidermal rete ridge collar encircles the hair shaft and contains approximately 200 Merkel cell-neurite complexes. Numerous other Merkel cell-neurite complexes are present in the external root sheath of the hair follicle beneath a thick glassy membrane innervated by approximately 65 nerve fibers. At this level 10-15 lanceolate or palisade terminals are situated in the connective tissue. Up to 10 simple encapsulated corpuscles can be identified above the level of lanceolate endings and Merkel cell terminals. Ruffini corpuscles are closely applied to the glassy membrane below the lanceolate and Merkel terminals at the level where nerve fibers penetrate the capsule of the sinus. All of these terminals are supplied by 80-100 large diameter myelinated fibers distributed approximately as follows: 65 innervate Merkel cell-neurite complexes, 15 to lanceolate, 10 to simple corpuscles, and 10 to Ruffini corpuscles. The innervation of the rete ridge collar is independent of that of the sinus consisting of 10-12 fibers derived from the superficial dermal network. Each of these sensory terminals can be correlated with specific functional parameters as described in numerous neurophysiologic studies. Merkel cell-neurite complexes and Ruffini corpuscles ae slowly adapting receptors; lanceolate terminals and simple corpuscles are rapidly adapting receptors.

The present study describes a complex array of sensory nerve terminals in the human eyelid. In many respects this pattern of innervation resembles that previously described in the rhesus monkey, but in other respects it is unique to man. The most prominent nerve terminals are a complex array of lanceolate and circular Ruffini and free nerve endings that envelop the eyelashes. In addition, Merkel cells have not been conclusively identified to date in other nonhuman primate nonsinus hairs. The external root sheath collar contains Merkel cells, and dermal Merkel cells have also been identified close to the collar. The anterior cutaneous surface of the eyelid contains small vellus hairs with typical lanceolate, Ruffini, and free nerve endings resembling those of primate facial skin. Scattered Meissner and scant simple corpuscles as well as scattered free nerve endings (FNEs) can be identified on the occlusal surface of the eyelid. Intraepithelial as well as dermal FNEs were most easily identified in this region in areas lacking other corpuscular receptors. Corpuscular receptors are especially common at the occlusal/conjunctival angle. The inner or conjunctival surface of the eyelid appears to be a glandular epithelium, whereas in the rhesus monkey it is stratified squamous epithelium. This epithelium needs additional study. In summary, the present study confirms the unique sensory neural status of the human eyelid and verifies the presence of Ruffini nerve terminals by light and electron microscopy and of free nerve ending terminals at least by light microscopy, as well as a unique pattern of innervation of the human eyelash.

The skin of primate eyelid contains three distinctive sensory nerve terminals. Small down hairs have a collar of lanceolate terminals that are formed by ramifications of the six to eight myelinated afferent fibers. Extensions of Schwann-cell cytoplasm form masses of cytoplasmic lamellae associated with these terminals. Every large hair or eyelash contains a large pilo-Ruffini as well as sparse lanceolate terminals. The eyelash Ruffini corpuscle resembles those of monkey facial guard hairs, sinus hairs, and joint capsules of the cat and pigeon. Sparse lanceolate terminals present between the Ruffini corpuscle and eyelash external root sheath resemble those of vellus hairs. On rare occasion Merkel cells are present in the hair follicle external root sheath above the sebaceous gland. Merkel touch spots, or Tastscheiben, are located between contiguous eyelashes as small rete pegs containing several Merkel cell-neurite complexes innervated by one or two myelinated afferent fibers. The function of this array of sensory terminals is presumed to represent an extensive mechanism of protection for the cornea and globe. On the basis of studies reported to date we can conclude that the Ruffini corpuscles (and related receptors) are the ubiquitous mechanoreceptors of cutaneous and musculoskeletal systems in birds as well as mammals.