Peau | EPFL Graph Search

vignette|Photographie rapprochée de la peau humaine. vignette|Dermatome (chaque couleur correspond à la partie de la peau innervée par un nerf différent, à partir de la moelle épinière). La peau (, provenant du pellis) est un organe composé de plusieurs couches de tissus. Elle est la première barrière de protection de l’organisme chez les Chordés. C’est l’organe le plus étendu et le plus lourd du corps humain ; chez l’adulte sa surface est d’environ , l’épaisseur varie de . Sa surface d’échange est cependant bien plus petite que celles de l’intestin (, environ deux terrains de tennis) et du poumon (). La dermatologie est la spécialité médicale qui traite les affections de la peau. Un traitement médical basé sur une substance active qui doit être administrée en lui faisant traverser la peau est dit « percutané ». Caractéristiques vignette|Dans le monde animal la peau des myxines est parmi les plus lâches et souples. Elle leur permet de passer au travers d’orifices très

Asymmetric Cell Division in the Skin

Wan-Hung Fan

An asymmetric cell division (ACD) is defined as a division that gives rise to two daughter cells with different fates. It is the most common type of division during development. Analogous to Drosophila neuroblasts, proteins involved in ACD such as Insc and LGN are found to be asymmetrically localized during perpendicular cell divisions in mammalian skin, suggesting that the cutaneous tissue homeostasis may be controlled by using similar mechanisms. Most cell divisions in the basal layer of the skin are perpendicular to the basal membrane (BM), but when a skin tumor is formed, most cell divisions would become parallel to the BM. Previous studies in our lab have shown that regressing skin tumor caused by β-catenin depletion have increased perpendicular cell divisions accompanied by reduced stem cell numbers and enhanced mTrim2 expression. Furthermore, induced expression of mTRIM2 in skin tumors led to tumor regression. Taken together, this suggests that progenitor cells in the basal layer of the epidermis may use vertical ACDs to maintain progenitor cell number while using horizontal SCDs to expand progenitor cell number and mTrim2 may function as a cell fate determinant in skin. To validate the hypothesis that vertical divisions of basal keratinocytes to the BM are ACDs, I utilized light sheet based fluorescence microscopy (LSFM) to perform the time lapse recording of murine embryonic skin development between E14.5 and E17.5 and to monitor individual dividing cells and to track their fates after division. For visualizing the dividing cells, protein localization and differentiating cells, I have generated several transgenic mouse lines and combined them together. My study showed that ACD of basal keratinocytes can be either vertical or horizontal to the BM and divisions in the suprabasal layer can be both ACDs and SCDs. To study the potential function of mTRIMs in skin, I generated the knock-out (KO) mice. Neither mTrim2 KO, mTrim3 KO or mTrim32 KO mice showed any phenotype in skin, therefore I combined these mice to generate mTrim2/3 double KO and mTrim2/3/32 triple KO mice. Still, no skin phenotype was observed in these mice, indicating that mTrim2/3/32 might not function as a cell fate determinant in skin.

EPFL2012

Epithelial stem cells and mechanical signal transduction

Vincent Bernard Cattin

Hair follicles are cutaneous structures characteristic of mammals. These sensitive organs cycle and contain multipotent epithelial stem cells which are implicated in hair growth and hair cycle. A single whisker follicle of the rat hosts up to 1500 stem cells, many more than necessary to regenerate the entire follicle throughout the animal's life. These cells are preferentially located in the most innervated region of the hair follicle. We hypothesised that stem cells might have an additional function aside from tissue renewal: stem cells may be involved in the mechanical signal transduction between hair follicle and afferent nervous system. This supplemental role may either take place through the interaction of the multipotent epithelial stem cells with nerve endings, or through neuroepithelial Merkel cells acting as intermediates. Merkel cells are located in the basal layer of the whisker follicle outer root sheath (ORS) and share a close relationship with their neighbouring nerve endings. These cells specifically express the transcription factor Math1 and their function is poorly understood. We demonstrate here by clonal analysis and transplantation assays that Merkel cells are not derived from epithelial stem cells. In addition, Math1-expressing cells isolated from the epidermis are unable to form colonies and to participate in the generation epidermal lineages when transplanted, failing to show stemness properties. Furthermore, when cultured in conditions that favour the growth of neurospheres, they are unable to proliferate, revealing a different behaviour than that of skin-derived neural crest cells. We also demonstrate that multipotent epithelial stem cells express several proteins implicated in glutamate neurotransmission, as well as other molecules usually found in the nervous system. The expression of NMDAR and AMPAR subunits, as well as their scaffolding proteins and neurotransmitter vesicular transport-implicated proteins are uncovered for the first time in the multipotent epithelial stem cells from the bulge. Our results support the mechanical signal transduction hypothesis and confirm the increasingly important role of the recently described neural-like structures of the skin. This work paves the way for a better comprehension of multipotent epithelial stem cell behaviour and stem cell-related pathologies.

EPFL2008