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Abstract Mesotrypsin, encoded by the PRSS3 gene, is a distinctive trypsin isoform renowned for its exceptional resistance to traditional trypsin inhibitors and unique substrate specificity. Within the skin epidermis, this protein primarily expresses in the upper layers of the stratified epidermis and plays a crucial role in processing pro-filaggrin (Pro-FLG). Although prior studies have partially elucidated its functions using primary cultured keratinocytes, challenges persist due to these cells' differentiation-activated cell death program. In the present study, HaCaT keratinocytes, characterized by minimal endogenous mesotrypsin expression and sustained proliferation in differentiated states, were utilized to further scrutinize the function of mesotrypsin. Despite the ready degradation of the intact form of active mesotrypsin in these cells, fusion with Venus, flanked by a peptide linker, enables evasion from the protein elimination machinery, thus facilitating activation of the Pro-FLG processing system. Inducing Venus-mesotrypsin expression in the cells resulted in a flattened phenotype and reduced proliferative capacity. Moreover, these cells displayed altered F-actin assembly, enhanced E-cadherin adhesive activity, and facilitated tight junction formation without overtly influencing epidermal differentiation. These findings underscore mesotrypsin's potentially pivotal role in shaping the characteristic cellular morphology of upper epidermal layers.

Background: Seborrheic keratosis (SK) is a skin condition affecting the keratinocytes. Although various treatment options are available, the need for a simpler topical treatment approach is unmet. Hydrogen peroxide (HP) acts by forming free radicals and initiates apoptosis in cells. Aims and Objectives: The aim of this study was to evaluate the safety and efficacy of 30% HP in SK. Materials and Methods: This study was conducted on patients attending the Dermatology, Venereology, and Leprology at MGM Hospital attached to Kakatiya Medical College, Warangal and Government Medical College Mahabubabad, Telangana, during the period from December 2019 to May 2021. In total, 80 adult patients with SKs were enrolled. The study was approved by the Research Ethics Committee of the MGM Hospital attached to Kakatiya Medical College. This is a prospective and interventional study. Eighty patients will be treated with 30% of HP topically. A photographic record of the pre- and post-treatment appearance of lesions was maintained. Physician’s lesion assessment (PLA) score was evaluated on day 15th and 106th day after treatment. Local skin reactions (LSRs) were divided into mild, moderate, and severe categories. LSR was observed immediately after 2 weeks and 106 days of treatment. Results: Most of the patients were of middle to elderly age group. SK lesions were most common seen over the head and trunk. The dermatosis papulosa nigra variant was the most common. PLA 0 was observed by day 15 in some patients after application. Of 30% HP, faster healing rates were observed in lesions over the face, and middle aged. Conclusion: About 30% HP is a promising option for the treatment of SK.

Abstract Backgrounds The detection of biomarkers of a stress response in the stratum corneum (SC) could be used as objective assessment of early stress symptoms and monitoring of stress reduction interventions in health care workers (HCWs). Aim The aim of this study is to explore SC biomarkers of immune and hormonal response and skin barrier for assessment of psychological distress (PD) in HCWs. Methods Twenty‐five female HCWs and 25 non‐HCWs participated. SC samples were collected using adhesive tapes at baseline and 3−5 days later (T1). We analyzed 24 biomarkers (immunological, vascular, hormones, and natural moisturizing factors). Stress symptoms were assessed using three scales of Copenhagen Psychosocial Questionnaire. The study involved: identifying SC biomarkers, correlating stress symptoms and biomarkers at baseline and T1, examining stress symptoms between the groups with a Mann‐Whitney test, comparing stress symptoms and biomarkers between groups using Ordinary Least Regression and investigating temporal variability of SC biomarkers at baseline and T1 using a Wilcoxon‐signed rank. Results Fourteen SC biomarkers were identified. We found correlations between general stress and “IL18” (r = 0.55) physical stress and “IL1b” (r = 0.36) and cognitive stress and “MIP3a” (r = 0.38) at baseline and general stress and cortisol (r = −0.49), physical stress and cortisol (r = −0.60) and cortisone (r = −0.67) at T1. We found no differences in stress symptoms and biomarkers between the groups, except for “MIP3a” at baseline. Differences in the biomarker levels between two time points were found for “TARC,” “VEGFA,” “ILRA,” “IL1RA/IL1a,” “NMF,” and “DHEA.” Conclusion The SC can be suitable biological material to assess biomarkers related to immune response, hormonal response, and skin barrier function. The SC biomarkers, showed strong, moderate and weak correlations with stress symptoms. Notably, these associations include cytokines of innate immunity and well‐known stress hormones, cortisol and cortisone.

Oriented cell divisions balance self-renewal and differentiation in stratified epithelia such as the skin epidermis. During peak epidermal stratification, the distribution of division angles among basal keratinocyte progenitors is bimodal, with planar and perpendicular divisions driving symmetric and asymmetric daughter cell fates, respectively. An apically restricted, evolutionarily conserved spindle orientation complex that includes the scaffolding protein LGN/Pins/Gpsm2 plays a central role in promoting perpendicular divisions and stratification, but why only a subset of cell polarize LGN is not known. Here, we demonstrate that the LGN paralog, AGS3/Gpsm1, is a novel negative regulator of LGN and inhibits perpendicular divisions. Static and ex vivo live imaging reveal that AGS3 overexpression displaces LGN from the apical cortex and increases planar orientations, while AGS3 loss prolongs cortical LGN localization and leads to a perpendicular orientation bias. Genetic epistasis experiments in double mutants confirm that AGS3 operates through LGN. Finally, clonal lineage tracing shows that LGN and AGS3 promote asymmetric and symmetric fates, respectively, while also influencing differentiation through delamination. Collectively, these studies shed new light on how spindle orientation influences epidermal stratification.

Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remain poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk and loss of Ectodysplasin signaling, which prevents dermal appendage formation, reduces Merkel cell density by affecting cell differentiation. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

Skin is an active immune organ where professional antigen-presenting cells such as epidermal Langerhans cells (LCs) link innate and adaptive immune responses. While Reticulon 1A (RTN1A) was recently identified in LCs and dendritic cells in cutaneous and lymphoid tissues of humans and mice, its function is still unclear. Here, we studied the involvement of this protein in cytoskeletal remodeling and immune responses toward pathogens by stimulation of Toll-like receptors (TLRs) in resident LCs (rLCs) and emigrated LCs (eLCs) in human epidermis ex vivo and in a transgenic THP-1 RTN1A+ cell line. Hampering RTN1A functionality through an inhibitory antibody induced significant dendrite retraction of rLCs and inhibited their emigration. Similarly, expression of RTN1A in THP-1 cells significantly altered their morphology, enhanced aggregation potential, and inhibited the Ca2+ flux. Differentiated THP-1 RTN1A+ macrophages exhibited long cell protrusions and a larger cell body size in comparison to wild-type cells. Further, stimulation of epidermal sheets with bacterial lipoproteins (TLR1/2 and TLR2 agonists) and single-stranded RNA (TLR7 agonist) resulted in the formation of substantial clusters of rLCs and a significant decrease of RTN1A expression in eLCs. Together, our data indicate involvement of RTN1A in dendrite dynamics and structural plasticity of primary LCs. Moreover, we discovered a relation between activation of TLRs, clustering of LCs, and downregulation of RTN1A within the epidermis, thus indicating an important role of RTN1A in LC residency and maintaining tissue homeostasis.

El síndrome de piel escaldada estafilocócica, la escarlatina estafilocócica y el impétigo ampollar son patologías que tienen en común el mecanismo de lesión de la piel por toxinas exfoliativas producidas por estafilococos, su presentación y manifestaciones clínicas son difíciles de diferenciar de otras patologías sistémicas como la enfermedad de Kawasaki, el síndrome de Steven Johnson y diferentes farmacodermias. En los últimos años se ha podido explicar el mecanismo molecular de lesión cutánea, lo que ayudo de manera importante a interpretar y poder realizar un adecuado diagnóstico diferencial entre estas patologías. Los pediatras necesitan múltiples herramientas para llegar a un diagnóstico certero de las noxas que producen lesiones en piel y manifestaciones sistémicas. Una buena anamnesis y el conocimiento de un abanico de diagnósticos diferenciales son importantes para el tratamiento médico.

Gongronema latifolium Benth belongs to the family Apocynaceae. Generally, the leaves and stems of G. latifolium are used as medicine and spices for sauces, soups and salads in Southern Nigeria. In view of its medicinal uses, the present study aimed at documenting anatomical characters and physicochemical properties for its standardization. The leaf epidermis, transverse section of the midrib, petiole and stem were prepared using standard procedures. Physicochemical properties of the powdered plant were conducted following standard methods. The leaf epidermal layer revealed anomocytic stomata, calcium oxalate crystals (rosette), uniseriate multicellular trichome (nonglandular). The midrib has an abundantly non glandular trichome with numerous rosette crystals. The percentage extractive values for ethanol, distilled water and petroleum ether in the leaf powder were 16.71±0.53, 13.24±0.71 and 2.08±0.13%, respectively, while that of stem were 12.51±0.15, 10.90±0.53 and 1.10±0.21, respectively. The moisture content and total ash values for the leaf powder were 11.45±0.53 and 9.70±0.17%, respectively while for the stem were 11.07±0.38 and 7.50±0.05, respectively. In the light of frequent consumption and use of G. latifolium as medicine, some of the pharmacognostic standards provided herein may be useful for its proper identification and subsequent compilation in a monograph. [ABSTRACT FROM AUTHOR]

Abstract Background For circadian medicine to influence health, such as when to take a drug or undergo a procedure, a biomarker of molecular clock phase is required––one that is easily measured and generalizable across a broad population. It is not clear that any circadian biomarker yet satisfies these criteria. Methods We analyzed 24-h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal (n = 20) and population (n = 154) data. We applied cyclic ordering by periodic structure (CYCLOPS) to order the population samples where biopsy time was not recorded. With CYCLOPS-predicted phases, we used ZeitZeiger to discover potential biomarkers of clock phase. Results Circadian clock function was strongest in the epidermis, regardless of body site. We identified a 12-gene expression signature that reported molecular clock phase to within 3 h (mean error = 2.5 h) from a single sample of epidermis––the skin’s most superficial layer. This set performed well across body sites, ages, sexes, and detection platforms. Conclusions This research shows that the clock in epidermis is more robust than dermis regardless of body site. To encourage ongoing validation of this putative biomarker in diverse populations, diseases, and experimental designs, we developed SkinPhaser––a user-friendly app to test biomarker performance in datasets ( https://github.com/gangwug/SkinPhaser ).

Introduction: Biomechanical properties of the skin change with pathological conditions and aging process. Nasolabial fold (NLF) is a degenerative manifestation of the skin tissue, which facilitates biomechanical properties measurement due to its quantifiable scales. The aim of this study was to evaluate the effectiveness of dry needling on decreasing NLF dimensions and improving NLF skin biomechanical properties. Materials and methods: 11 women aged between 35-55 years with NLF class between 2-2.5 were selected for study, and received 7 sessions of dry needling treatment. Another group of young women between 20-30 years considered as control group and received no treatment. NLF depth and area, epidermis and dermis thickness, and young modulus of NLF skin were analyzed with high resolution ultrasonography and a custom-made forceguage. For reliability of sonographic data the interclass correlation coefficient, and for between and within group comparisons, independent and paired t tests were used, respectively. Results: NLF depth and area decreased significantly (P < 0.001). Moreover, epidermis and dermis thickness and young modulus increased significantly (P < 0.001). Conclusion: Dry needling induced decrease in depth and area, and improved biomechanical properties of the NLF, without any side effect.

Abstract New autologous skin regeneration technology yielded full‐thickness skin as evidenced by clinical observation and skin biopsy 5 months after surgery, providing relief for debilitating split‐thickness skin graft contracture in a pediatric burn case.

Different melanoma subtypes exhibit specific and non-overlapping sets of oncogene and tumor suppressor mutations, despite a common cell of origin in melanocytes. For example, activation of the Gαq/11 signaling pathway is a characteristic initiating event in primary melanomas that arise in the dermis, uveal tract, or central nervous system. It is rare in melanomas arising in the epidermis. The mechanism for this specificity is unknown. Here, we present evidence that in the mouse, crosstalk with the epidermal microenvironment actively impairs the survival of melanocytes expressing the GNAQQ209L oncogene. We found that GNAQQ209L, in combination with signaling from the interfollicular epidermis (IFE), stimulates dendrite extension, leads to actin cytoskeleton disorganization, inhibits proliferation, and promotes apoptosis in melanocytes. The effect was reversible and paracrine. In contrast, the epidermal environment increased the survival of wildtype and BrafV600E expressing melanocytes. Hence, our studies reveal the flip side of Gαq/11 signaling, which was hitherto unsuspected. In the future, the identification of the epidermal signals that restrain the GNAQQ209L oncogene could suggest novel therapies for GNAQ and GNA11 mutant melanomas.

Objective: To compare the age related changes in thickness of skin epidermis in different age groups in the Pakistani population. Study Design: Cross sectional study. Place and Duration of Study: The study was conducted at Army Medical College, Rawalpindi, for a period of five months, from Jul 2010 to Nov 2010. All protocols were approved by the Ethical committee of centre for research in experimental and applied medicine (CREAM), Army Medical College, Rawalpindi. Patients and Methods: In this study, 60 volunteers of both genders, fulfilling the inclusion criteria, were divided according to age, into three equal groups, 18-29 years, 30-49 years, and more than 50 years, Groups A, B and C respectively. All study participants gave written consent before their inclusion in the study Four-mm full-thickness punch biopsy of sun protected upper arm skin of left side was obtained from each individual after administration of local anesthetic injection. The samples were stained with Haematoxylin and Eosin for histomorphological study and comparison of epidermal thickness was done between the three groups. In each section, the epidermal thickness was measured at three points to determine maximum thickness, under 10X objective. Mean of three readings of each sample was taken. Then, mean of each group was taken and that of the three groups was compared to determine the presence or absence of epidermal atrophy. Results: There was no appreciable difference in epidermal thickness between the three groups. Mean of group A was 144.833 μm, that of group-B was 142.833 μm and the mean value of group C was 125.5 μm. Conclusion: It was concluded that, although human skin markedly deteriorates visibly with age, the epidermal thickness remains constant.

While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through linker of nucleoskeleton and cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.

To orchestrate collective polarization across tissues, planar cell polarity (PCP) proteins localize asymmetrically to cell junctions, a conserved feature of PCP that requires the atypical cadherin Celsr1. We report that mouse Celsr1 engages in both trans- and cis-interactions, and organizes into dense and highly stable punctate assemblies. We provide evidence suggesting that PCP-mutant variant of Celsr1, Celsr1Crsh, selectively impairs lateral cis-interactions. Although Celsr1Crsh mediates cell adhesion in trans, it displays increased mobility, diminishes junctional enrichment, and fails to engage in homophilic adhesion with the wild-type protein, phenotypes that can be rescued by ectopic cis-dimerization. Using biochemical and super-resolution microscopy approaches, we show that although Celsr1Crsh physically interacts with PCP proteins Frizzled6 and Vangl2, it fails to organize these proteins into asymmetric junctional complexes. Our results suggest mammalian Celsr1 functions not only as a trans-adhesive homodimeric bridge, but also as an organizer of intercellular Frizzled6 and Vangl2 asymmetry through lateral, cis-interactions.

The ability of epithelial tissues to heal after injury is essential for animal life, yet the mechanisms by which epithelial cells sense tissue damage are incompletely understood. In aquatic organisms such as zebrafish, osmotic shock following injury is believed to be an early and potent activator of a wound response. We find that, in addition to sensing osmolarity, basal skin cells in zebrafish larvae are also sensitive to changes in the particular ionic composition of their surroundings after wounding, specifically the concentration of sodium chloride in the immediate vicinity of the wound. This sodium chloride-specific wound detection mechanism is independent of cell swelling, and instead is suggestive of a mechanism by which cells sense changes in the transepithelial electrical potential generated by the transport of sodium and chloride ions across the skin. Consistent with this hypothesis, we show that electric fields directly applied within the skin are sufficient to initiate actin polarization and migration of basal cells in their native epithelial context in vivo, even overriding endogenous wound signaling. This suggests that, in order to mount a robust wound response, skin cells respond to both osmotic and electrical perturbations arising from tissue injury.

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient's quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient's response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.

The intermediate filament protein keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at Krt14’s codon 373 (C373A) exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in epidermis. A proteomics screen identified 14-3-3 as K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14 C373A keratinocytes. Residue C373 in K14, which is conserved in a subset of keratins, is revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in epidermis.

Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events. We report that two LIN-29 isoforms fulfill distinct functions. Functional specialization is a consequence of distinct isoform expression patterns, not protein sequence, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique isoform expression patterns are generated by the activities of LIN-41 for lin-29a, and of HBL-1 for lin-29b, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both hbl-1 and lin-41. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

The epidermis, a multilayered epithelium, surrounds and protects the vertebrate body. It develops from a bilayered epithelium formed of the outer periderm and underlying basal epidermis. How apicobasal polarity is established in the developing epidermis has remained poorly understood. We show that both the periderm and the basal epidermis exhibit polarised distribution of adherens junctions in zebrafish. aPKC, an apical polarity regulator, maintains the robustness of polarisation of E-cadherin- an adherens junction component- in the periderm. E-cadherin in one layer controls the localisation of E-cadherin in the second layer in a layer non-autonomous manner. Importantly, E-cadherin controls the localisation and levels of Lgl, a basolateral polarity regulator, in a layer autonomous as well non-autonomous manner. Since periderm formation from the enveloping layer precedes the formation of the basal epidermis, our analyses suggest that peridermal polarity, initiated by aPKC, is transduced in a stepwise manner by E-cadherin to the basal layer.

The article presents modern data on the ontogenesis of the skin, the formation of all its elements and structures during prenatal development and postnatal period. The modern ideas about the features of the structure of the skin in the newborn and infant are highlighted in detail. Particular attention is paid to the protective mechanisms of the skin, providing a mechanical barrier, and factors of innate immunity, lipids, as well as skin microbiome. Much attention is paid to the importance of the dampening for the skin of the fetus and newborn, as well as the processes of adaptation of the skin of the newborn to the extrauterine environment. The modern recommendations for skin care, based on data of the features of the development, structure and functioning of the skin of the newborn and infant are presented.

Introduction: Although it is important to know the normal values of dermis, epidermis, or total skin thicknesses (ST) for some drugs and vaccine research, skin-related clinical investigations, and skin transfer operations used in plastic surgery, it would not be ethical to take new biopsies from healthy volunteers to measure their ST. This study aims to describe a new ethical histometric technique for the measurement of skin layers and to determine the mean ST of some major body regions in the people living in our region. Materials and Methods: A total of 180 skin samples from six major body regions of 90 males and 90 females were enrolled in the study. The measurements were performed histometrically from appropriate skin samples obtained from the pathology archive. The samples were classified according to the six different parts of the body (scalp, abdomen, back, dorsum of foot, dorsum of hand, and the breast). Results: The mean epidermal thickness ranged from 76.9 ± 26.2 to 267.4 ± 120.6 μm. The thickest epidermis was found in the dorsum of foot in women (267.4 ± 120.6 μm) while the thinnest was found in the breast in women (76.9 ± 26.2 μm). The mean dermal thickness ranged from 2115 ± 946.4 to 5888 ± 2422.3 μm. The thickest dermis was found in the breast in men (5888 ± 2422.3 μm), while the thinnest dermis was found in the dorsum of hand in women (2115 ± 946.4 μm). Conclusions: Human ST varies according to ethnic origin. It was determined that the dermis and epidermis of Anatolian people are thicker than that of the previously reported other ethnic groups. The skin pathology archive can be used to create maps of the body's skin structure.

Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.

The control of cell fate through oriented cell division is imperative for proper organ development. Basal epidermal progenitor cells divide parallel or perpendicular to the basement membrane to self-renew or produce differentiated stratified layers, but the mechanisms regulating the choice between division orientations are unknown. Using time-lapse imaging to follow divisions and fates of basal progenitors, we find that mouse embryos defective for the planar cell polarity (PCP) gene, Vangl2, exhibit increased perpendicular divisions and hyperthickened epidermis. Surprisingly, this is not due to defective Vangl2 function in the epidermis, but to changes in cell geometry and packing that arise from the open neural tube characteristic of PCP mutants. Through regional variations in epidermal deformation and physical manipulations, we show that local tissue architecture, rather than cortical PCP cues, regulates the decision between symmetric and stratifying divisions, allowing flexibility for basal cells to adapt to the needs of the developing tissue.

Interactions between epithelial cells and neurons influence a range of sensory modalities including taste, touch, and smell. Vertebrate and invertebrate epidermal cells ensheath peripheral arbors of somatosensory neurons, including nociceptors, yet the developmental origins and functional roles of this ensheathment are largely unknown. Here, we describe an evolutionarily conserved morphogenetic mechanism for epidermal ensheathment of somatosensory neurites. We found that somatosensory neurons in Drosophila and zebrafish induce formation of epidermal sheaths, which wrap neurites of different types of neurons to different extents. Neurites induce formation of plasma membrane phosphatidylinositol 4,5-bisphosphate microdomains at nascent sheaths, followed by a filamentous actin network, and recruitment of junctional proteins that likely form autotypic junctions to seal sheaths. Finally, blocking epidermal sheath formation destabilized dendrite branches and reduced nociceptive sensitivity in Drosophila. Epidermal somatosensory neurite ensheathment is thus a deeply conserved cellular process that contributes to the morphogenesis and function of nociceptive sensory neurons.

Introduction: With the proliferation of electrical equipment and devices, there is a rise in deaths due to electrocution injuries. There may be allegations of electric burns either by way of accident or torture. Many a times no specific findings may be present to support such a claim. Electric contact mark is pathognomic of electrocution. Aim: To decide whether the electric current mark was antemortem or postmortem in nature or no conclusion regarding the same can be drawn even after histopathological examination. Materials and Methods: The present study was conducted on 40 dead bodies brought to the mortuary of a Tertiary Care Institution, Government Medical College, Amritsar, Punjab, India, with history of death due to electric shock over a period of two years. Another 20 corpses, who had not died due to electric current injury, but were given the same after death, were taken as control. All the 40 cases were thoroughly examined for medicolegal purposes at the time of conducting postmortem examination and findings were recorded as per proforma attached. Skin was examined for the wound of entry and exit (if any) of electric current injury. Skin biopsies, from the electric current sites of the deceased, were taken from the edge of the wound and subjected to histopathological examination. Results: About 85% cases had visible electric current injury. Involvement of clothes was seen in 15% cases. Microscopic findings included bulla (22.5%), flattened papillae (47.5%), erosions (12.5%), charring (45%), nuclear changes (2.5%), vacuolisation (12.5%) and necrosis (62.5%). In the 20 control cases studied, charring of the skin was present in the epidermis/ dermis and no other change was observed. Conclusion: Histopathological changes can be used as supportive evidence in giving cause of death in such cases.

The first point of our body’s contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.