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While fibroblast growth factor (FGF) 23 is known as a phosphaturic factor in inherited and/or acquired hypophosphatemic disorders, it also serves an endocrine role in normal phosphate homeostasis. FGF23 acts negatively on the NaPi2a cotransporter and 25-hydroxy D(3)-1 alpha-hydroxylase with a resultant decrease in renal phosphate (Pi) reabsorption, while osteoblasts appear to be a primary source of FGF23 whose expression is counter-upregulated by 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Here we have shown the distribution of FGF23 in normal rat bone and tooth, and its expression profile in fetal rat calvaria (RC) cell cultures. FGF23 mRNA was detectable in multiple fetal and adult tissues but levels were much higher in adult calvaria, femur and incisor, compared to the other tissues tested. Immunoreactive FGF23 was predominantly localized to osteoblasts, cementoblasts, and odontoblasts, with sporadic labeling in some chondrocytes, osteocytes and cementocytes. Notably, osteoclasts were also found to be a possible source of FGF23. Fetal bone and tooth germ cells labeled much less intensely than young adult osteoblasts and odontoblasts. In the RC cell model, FGF23 was expressed during osteoblast development. During matrix mineralization induced by beta-glycerophosphate (beta GP), FGF23 expression was transiently upregulated and then decreased to levels lower than in their non-beta GP-treated counterparts. 1,25(OH)(2)D(3) markedly increased FGF23 expression concomitant with the inhibition of beta GP-induced mineralization. Our data suggest that FGF23 expression in bone is closely correlated with bone formation in vitro and vivo, and points towards an important role(s) for FGF23 in young adult but not fetal mineralized tissues as a systemic factor for Pi homeostasis.

This study was conducted to investigate immunohistochemically the expression of c-Fos in neurons around the trigeminal motor nucleus following application of mechanical force to a tooth, a mechanical pinch to the tongue, and paraformaldehyde injection into the periodontal ligament and masseter muscle. Following the application of all of these stimuli except pinching the tongue, a small number of c-Fos-like immunoreactive (Fos-LI) neurons were found in the ipsilateral supratrigeminal region. c-Fos expression was also detected in numerous neurons in the superficial laminae of the subnucleus caudalis in all experimental animals. Induction of c-Fos in the subnucleus caudalis and the supratrigeminal region indicates that Fos-LI neurons in the supratrigeminal region are involved in the processing of intraoral nociceptive signals.

Osteopetrotic (op/op) mice show severe osteosclerosis caused by an inherited deficiency of osteoclast and resultant failure of tooth eruption, which can be cured by the injection of macrophage colony-stimulating factor (M-CSF). The present study revealed that consecutive injections of M-CSF in these mutant mice brought about a recovery of bone resorption resulting in the resumption of growth of tooth root and periodontal ligament. Bone resorption at the inner surface of bony crypts was noted on the 5th day after the start of M-CSF injections. This activity was reduced with the progress of root and periodontal ligament formation, being confined to the basal and crestal portion of bony crypts by the 15th day of the experiment. Second molars emerged into the oral cavity on the 15th day, but no eruption of first molars was observed until the 20th day. Throughout the experiment, first molars exhibited appreciable root deformity, which was less severe in second molars. Delayed eruption of first molars was thought to be related to the severity of the disturbance of root formation.

Although the optic nerve fibers of the cone-dominant ground squirrel retina have been well studied physiologically, the morphological details of the retinal neurons have not. To that end, retinal neurons of the California ground squirrel have been studied in Golgi-impregnated wholemounts. Two types of horizontal cell have been identified: H1 has an axon and axon terminal, whereas H2 is axonless. The dendritic field of H1 cells enlarges in a nonuniform manner with increasing displacement from the central retina. The smallest examples lie centrally in the visual streak, and the largest occur in the superior periphery. Eight types of bipolar cell are distinguished by morphological differences in dendritic branching pattern and field size in the outer plexiform layer, cell body size, and layering within the inner nuclear layer and by the morphology and stratification of axon terminals in the inner plexiform layer. A large bistratified bipolar cell (B8) is introduced here; the other 7 types closely resemble those in the retinas of other sciurid species described by R.W. West (1976, J. Comp. Neurol. 168:355-378; 1978, Vision Res. 18:129-136). The B1 type is proposed as a blue cone bipolar cell. Amacrine cells are classified into 27 cell types. Six of these occur as mirror-image pairs across the inner plexiform layer, the soma of one of each pair being "displaced" to the ganglion cell layer. The best described of these pairs is the very elaborate starburst amacrine cell, A5, which stains regularly in these wholemounted retinas. Changes in dendritic field size of both A5 subtypes with retinal location are quantified. The morphology of three amacrine cell types identified in Spermophilus beecheyi suggests that their possible counterparts in S. mexicanus (West, 1976) were, as displaced amacrine cells, misidentified as ganglion cells. Amacrine cell types that may play roles in the rod pathway, the blue cone pathway, and ganglion cell directional selectivity are discussed. No type of interplexiform cell was observed. Ganglion cells are classified into 19 cell types, 9 of which probably correspond to the ganglion cells described by West (1976) in the Mexican ground squirrel. The bistratified G11 cell is proposed as an ON-OFF directionally selective type.

Previous studies indicate that vibrissa, nonvibrissa, guard hair, hairy skin, and periodontal ligament afferents give rise to morphologically distinct terminal arbors in the trigeminal nuclei principalis (Vp) and oralis (Vo) in the cat. The present study describes the extent to which morphological and functional relationships exist in the nuclei interpolaris (Vi) and caudalis (Vc). Twenty-two fibers were physiologically characterized and stained by intra-axonal HRP injection techniques. The fast adapting (FA) vibrissa (VF) afferents gave rise to compact and circumscribed arbors in Vi and Vc. These tended to be larger in Vc than in Vi. The slowly adapting (SA) vibrissa (VS) afferents in Vi and Vc had more widespread and larger arbors than those of the VF afferents. The VS arbors in Vc tended to be larger and less circular than those in Vi. Guard hair (GH) afferents gave rise to circumscribed arbors in both nuclei, but those in Vc tended to have larger and more circular arbors than those in Vi. Down hair (DH) afferents gave rise to small, circumscribed arbors or a few distinct patches of boutons within a small area in Vi; arbors in Vc were less extensive and "stringy." Unlike other afferents, DH arbors were larger in Vi than in Vc, but smaller than those of GH afferents in either nuclei. The SA hairy skin (SS) afferents had arbors that were widespread with a few distinct patches of boutons; the arbors in Vc were larger than those in Vi. The arbors of SS afferents were smaller than those of VS and GH afferents in both nuclei. Like GH afferents, FA periodontal ligament (PF) afferents gave rise to large and circumscribed arbors in Vi, although the arbors in Vc were smaller and less dense. The present study demonstrated significant functional and morphological relationships for primary afferents in Vi and Vc, thus suggesting that sensory information from each of the distinct fiber or functional classes is processed in a characteristic manner in the individual nuclei.

Horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA) was injected into the trigeminal ganglion of adult rats to label the peripheral sensory receptors of the tongue. The conjugate was transported anterogradely to all the ipsilateral fungiform papillae and filiform papillae. Some labeled fibers crossed over to the contralateral papillae. In the intrinsic tongue muscle undulating nerve fibers along or across muscle fibers were often observed, and formed simple spiral endings.

Intra-axonal recording and horseradish peroxidase (HRP) injection techniques were employed to examine the response properties of low-threshold mechanoreceptive afferents and the morphological characteristics of their axon arbors in the main sensory nucleus (Vp) and oral nucleus (Vo). Thirteen afferents were characterized and recovered. One gave fast or rapidly adapting (FA) and 3 slowly adapting (SA) responses to mystacial vibrissa deflection, 5 were sensitive to deflection of non-vibrissae hairs or hair (4 were guard hair afferents and the other responded to deflection of a long hair in slowly adapting fashion) and two were responsive to indentation of the hairy skin. The remainder were responsive to indentation of the glabrous skin on the lower lip: one was of FA type and the other of SA type. All of the axons had bifurcating fibers that ascended in the ascending tract (ascending fiber) and descended in the trigeminal spinal tract (descending fiber). The main collaterals given off from the ascending fiber and rostral segment of the descending fiber terminated in the Vp, and the other collaterals from the descending fiber projected to the Vo. Terminal arbors produced by the main collaterals formed a rostrocaudally continuous column, but generally the adjacent arbors did not overlap except when pairs of collaterals arose near each other on the ascending and descending fibers. Projections of collaterals to Vp and Vo were organized topographically. The head was represented in an inverted fashion with its anteroposterior axis in a mediolateral sequence, but the lower glabrous lip was represented more dorsally than the other mandibular facial regions. Vibrissa afferents formed a rostrocaudally continuous, densely packed terminal column throughout the length of Vp and Vo. SA vibrissa afferents gave rise to more dense and roundish arbors in Vp than the FA afferent, while the Vo.c arbors were more compact and smaller than those of the FA afferent. Guard hair afferents had arbors that were highly variable throughout the nuclei and were characterized by less developed arbors in Vp than in Vo. Unlike vibrissa afferents, hairy skin afferents gave rise to sparse and widespread arbors characterized by a string-like appearance, while the Vo collaterals were more stringy. Facial lip afferents were characterized by a great difference in collateral morphology between FA and SA type.(ABSTRACT TRUNCATED AT 400 WORDS)

Retrograde and anterograde transport of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) conjugate was used to study the organization of primary afferent neurons innervating the masticatory muscles. HRP applied to the nerves of jaw-closing muscles--the deep temporal (DT), masseter (Ma), and medial pterygoid (MP)--labeled cells in the trigeminal ganglion and the mesencephalic trigeminal nucleus (Vmes), whereas HRP applied to nerves of the jaw-opening muscles--anterior digastric (AD) and mylohyoid (My)--labeled cells only in the trigeminal ganglion. Cell bodies innervating the jaw-closing muscles were found with greater frequency in the intermediate region of the mandibular subdivision, while somata supplying the jaw-opening muscles were predominant posterolaterally. The distribution of their somatic sizes was unimodal and limited to a subpopulation of smaller cells. Projections of the muscle afferents of ganglionic origin to the trigeminal sensory nuclear complex (TSNC) were confined primarily to the caudal half of pars interpolaris (Vi), and the medullary and upper cervical dorsal horns. In the Vi, Ma, MP, AD, and My nerves terminated in the lateral-most part of the nucleus with an extensive overlap in projections, save for the DT nerve, which projected to the interstitial nucleus or paratrigeminal nucleus. In the medullary and upper cervical dorsal horns, the main terminal fields of individual branches were confined to laminae I/V, but the density of the terminals in lamina V was very sparse. The rostrocaudal extent of the terminal field in lamina I differed among the muscle afferents of origin, whereas in the mediolateral or dorsoventral axis, a remarkable overlap in projections was noted between or among muscle afferents. The terminals of DT afferents were most broadly extended from the rostral level of the pars caudalis to the C3 segment, whereas the MP nerve showed limited projection to the middle one-third of the pars caudalis. Terminal fields of the Ma, AD, and My nerves appeared in the caudal two-thirds of the pars caudalis including the first two cervical segments, the caudal half of the pars caudalis and the C1 segment, and in the caudal part of the pars caudalis including the rostral C1 segment, respectively. This rostrocaudal arrangement in the projections of muscle nerves, which corresponds to the anteroposterior length of the muscles and their positions, indicates that representation of the masticatory muscles in lamina I reflects an onion-skin organization. These results suggest that primary muscle afferent neurons of ganglionic origin primarily mediate muscle pain.(ABSTRACT TRUNCATED AT 400 WORDS)

Thalamic projections from the caudal medulla of the cat were examined using the method of retrograde axonal transport of horseradish peroxidase (HRP). Injections were made unilaterally in various thalamic regions. Large injections labeled cells in the subnuclei: zonalis (Vcz), gelatinosus (Vcg), magnocellularis (Vcm), reticularis dorsalis (Vcrd) and ventralis (Vcv) medullae oblongatae. The largest number of labeled cells were in Vcz, Vcrd and Vcrv. Most of the labeled cells in Vcz and Vcrd were contralateral to the injection site, although the labeled cells in the Vcrv were bilateral. Small injections were made into the medial, lateral and dorsal regions of the nucleus ventralis posteromedialis (VPM), rostral regions of the posterior nuclei (POm and PO1), caudal POm, the nucleus centralis lateralis (CL) and the center median-parafascicular nuclear complex (CM-Pf). Most of the neurons in Vcz were found to project to the medial VPM and some to the caudal POm. A small number of cells in the Vcrd project to the medial VPM, but a large number project to the caudal POm and CM-Pf complex. The largest number of neurons projecting to the CM-Pf complex was present in Vcrv, where the labeled cells were bilateral. The types of trigeminothalamic projecting cells and the sizes of their somata were observed for different subnuclei and a considerable difference was found to exist among the subnuclei. This anatomical differentiation of the trigeminothalamic projections probably reflects a functional specialization of neuronal location since the functional properties of neurons vary according to their locations.

The morphology of single neurons in the trigeminal mesencephalic nucleus (Vmes) that innervate periodontal ligament was studied in cats by the method of intraaxonal injection of horseradish peroxidase (HRP). Two kinds of Vmes neurons were distinguished on the basis of differences in axon profile and its central projection. The first type of Vmes neurons was unipolar in shape and its axon was divided into united (U), peripheral (P), and central axons (C). The U axon traveled caudally within the Vmes from the soma to the dorsolateral aspect of trigeminal motor nucleus (Vmo), where it split into the P and C axons with a T-shaped appearance. The P axon joined the spinal trigeminal tract across the trigeminal principal nucleus and ran within the tract and sensory root to exit the brainstem. The C axon traveled caudally within Probst's tract. All 3 axons issued axon collaterals. Axon collaterals from the U, P and the proximal C axons sent their terminal branches into the supra (Vsup) and intertrigeminal regions (Vint). Most axon collaterals from the C axon sent their terminal branches into the juxtatrigeminal regions (Vjuxta). The second type of Vmes neurons was bipolar and issued P and C axons. The C axon ran a short distance in the Vmes to leave the Vmes, and then it traveled caudolaterally in the rostrodorsomedial aspect of the Vmo. Finally, it entered in the Vmo and traveled caudally in the dorsolateral subdivision of the nucleus to its rostrocaudal mid-level. The C axon gave off massive axon collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)