Talk:Integumentary System Development

Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network

Chorro L, Sarde A, Li M, Woollard KJ, Chambon P, Malissen B, Kissenpfennig A, Barbaroux JB, Groves R, Geissmann F. J Exp Med. 2009 Dec 21;206(13):3089-100. Epub 2009 Dec 7. PMID: 19995948

Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin(+) cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10-20-fold. After the first week of life, we observed low-level proliferation of langerin(+) cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.

PMID: 19995948 http://www.ncbi.nlm.nih.gov/pubmed/19995948

http://jem.rupress.org/content/206/13/3089.long

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

Elaine Fuchs: A love for science that's more than skin deep. Interviewed by Ben Short

Fuchs E. J Cell Biol. 2009 Dec 28;187(7):938-9. No abstract available. PMID: 20038675

http://www.ncbi.nlm.nih.gov/pubmed/20038675 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806278/?tool=pubmed

---

Biology and Genetics of Hair. http://www.ncbi.nlm.nih.gov/pubmed/20590427

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064709/?tool=pubmed

Development of a three dimensional multiscale computational model of the human epidermis

Adra S, Sun T, MacNeil S, Holcombe M, Smallwood R. PLoS One. 2010 Jan 14;5(1):e8511. PMID: 20076760

Transforming Growth Factor (TGF-beta1) is a member of the TGF-beta superfamily ligand-receptor network. and plays a crucial role in tissue regeneration. The extensive in vitro and in vivo experimental literature describing its actions nevertheless describe an apparent paradox in that during re-epithelialisation it acts as proliferation inhibitor for keratinocytes. The majority of biological models focus on certain aspects of TGF-beta1 behaviour and no one model provides a comprehensive story of this regulatory factor's action. Accordingly our aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-beta1. In our previous study, an agent-based model of keratinocyte colony formation in 2D culture was developed. In this study this model was extensively developed into a three dimensional multiscale model of the human epidermis which is comprised of three interacting and integrated layers: (1) an agent-based model which captures the biological rules governing the cells in the human epidermis at the cellular level and includes the rules for injury induced emergent behaviours, (2) a COmplex PAthway SImulator (COPASI) model which simulates the expression and signalling of TGF-beta1 at the sub-cellular level and (3) a mechanical layer embodied by a numerical physical solver responsible for resolving the forces exerted between cells at the multi-cellular level. The integrated model was initially validated by using it to grow a piece of virtual epidermis in 3D and comparing the in virtuo simulations of keratinocyte behaviour and of TGF-beta1 signalling with the extensive research literature describing this key regulatory protein. This research reinforces the idea that computational modelling can be an effective additional tool to aid our understanding of complex systems. In the accompanying paper the model is used to explore hypotheses of the functions of TGF-beta1 at the cellular and subcellular level on different keratinocyte populations during epidermal wound healing.

PMID: 20076760 http://www.ncbi.nlm.nih.gov/pubmed/20076760

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008511

Melanoblasts

Ex vivo live imaging of melanoblast migration in embryonic mouse skin.

Pigment Cell Melanoma Res. 2010 Apr;23(2):299-301. Epub 2010 Jan 7.

Mort RL, Hay L, Jackson IJ.

PMID: 20067551 http://www.ncbi.nlm.nih.gov/pubmed/20067551

Melanoblasts are the embryonic precursors of melanocytes. They are derived from the neural crest at around embryonic day 9.5 (E9.5) and upregulate early melanoblast specific markers (Mitf, Tyrosinase, Dct, Kit) around E10.5.

Includes videos of melanoblast migration in model mouse skin system.

The making of a melanocyte: the specification of melanoblasts from the neural crest.

Thomas AJ, Erickson CA. Pigment Cell Melanoma Res. 2008 Dec;21(6):598-610. Review. PMID: 19067969

Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes

Development. 2009 Aug;136(15):2511-21. Epub 2009 Jun 24.

Aoki H, Yamada Y, Hara A, Kunisada T.

Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan. Abstract Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear - the so-called non-cutaneous melanocytes - remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.

PMID: 19553284 http://www.ncbi.nlm.nih.gov/pubmed/19553284