Talk:Integumentary System Development
Comparison between human fetal and adult skin
Coolen NA, Schouten KC, Middelkoop E, Ulrich MM. Arch Dermatol Res. 2010 Jan;302(1):47-55. Epub 2009 Aug 23. PMID: 19701759 http://www.ncbi.nlm.nih.gov/pubmed/19701759
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799629
http://www.springerlink.com/content/lv415257322x8247 http://www.springerlink.com/content/lv415257322x8247/fulltext.html
Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22 weeks’ gestation) and adult skin biopsies, the expression patterns of several epidermal proteins (K10, K14, K16, K17, SKALP, involucrin), basement membrane proteins, Ki-67, blood vessels and extracellular matrix proteins (fibronectin, chondroitin sulfate, elastin) were determined using immunohistochemistry. The expression profiles of K17, involucrin, dermal Ki-67, fibronectin and chondroitin sulfate were higher in the fetal skin than in adult skin. In the fetal skin, elastin was not present in the dermis, but it was found in the adult skin. The expression patterns of basement membrane proteins, blood vessels, K10, K14, K16 and epidermal Ki-67 were similar in human fetal skin and adult skin. In this systematic overview, most of the differences between fetal and adult skin were found at the level of dermal extracellular matrix molecules expression. This study suggests that, especially, dermal components are important in fetal scarless healing.
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
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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
Vernix caseosa
Unraveling the mystery of vernix caseosa
Indian J Dermatol. 2008;53(2):54-60.
Singh G, Archana G.
Department of Dermatology and STD, Sri Devaraj Urs Medical College, Tamaka, Kolar - 563 101, India. drsinghgs@gmail.com Abstract Vernix caseosa is a white, creamy, naturally occurring biofilm covering the skin of the fetus during the last trimester of pregnancy. Vernix coating on the neonatal skin protects the newborn skin and facilitates extra-uterine adaptation of skin in the first postnatal week if not washed away after birth. It consists of water-containing corneocytes embedded in a lipid matrix. The strategic location of the vernix on the fetal skin surface suggests participation in multiple overlapping functions required at birth, such as barrier to water loss, temperature regulation, and innate immunity. Vernix seems to perform various integral roles during transition of the fetus from intra-uterine to extra-uterine life. It has also found various interesting diagnostic and prognostic implications in this arena. Thus, it continues to be an intriguing topic of interest among the medical fraternity to understand its detailed biology and function in the fetus and also to put its naturally endowed characteristics to use in the adult population.
PMID: 19881987 http://www.ncbi.nlm.nih.gov/pubmed/19881987
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763724
Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions
Tollin M, Bergsson G, Kai-Larsen Y, Lengqvist J, Sjövall J, Griffiths W, Skúladóttir GV, Haraldsson A, Jörnvall H, Gudmundsson GH, Agerberth B. Cell Mol Life Sci. 2005 Oct;62(19-20):2390-9.
PMID: 16179970 http://www.ncbi.nlm.nih.gov/pubmed/16179970
http://www.springerlink.com/content/q31860t243485552/
Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection.
Vernix caseosa peritonitis - no longer rare or innocent: a case series
J Med Case Reports. 2009 Feb 10;3:60.
Stuart OA, Morris AR, Baber RJ.
Department of Women's & Children's Health, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW 2065, Australia. oliviastuart@yahoo.com. Abstract ABSTRACT:
INTRODUCTION: Vernix Caseosa peritonitis is a rare post caesarean section complication with only 19 case reports in the literature to date. Vernix caseosa spilt at the time of caesarean section is thought to incite an inflammatory reaction, causing symptoms resembling an acute abdomen.
CASE PRESENTATION: We discuss three Caucasian patients (aged 32 to 43 years) who presented in our health sector in Sydney with vernix caseosa peritonitis. Each had a protracted course with significant comorbidities requiring surgical and medical intervention. This contrasts with other reports suggesting that a rapid resolution can be expected.This cluster may be a consequence of the rising caesarean section rate, a heightened local awareness of the condition and possibly a result of leaving material in the paracolic gutters intraoperatively.
CONCLUSION: Our aim is to increase awareness among our obstetric and surgical colleagues of the characteristic clinical presentation and intra-operative findings of vernix caseosa peritonitis. We also point out that, in contrast to those presented here, not all patients require laparotomy.
PMID: 19208257 http://www.ncbi.nlm.nih.gov/pubmed/19208257
Contamination of caesarean wounds by Vernix caseosa.
MALPAS P.
Br Med J. 1950 Sep 30;2(4682):763. No abstract available.
PMID: 14772475
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
FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate
Development. 2009 May;136(10):1741-50. Epub 2009 Apr 15.
Huang J, Dattilo LK, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, Deng CX, Umans L, Zwijsen A, Roberts AB, Beebe DC.
Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA. Abstract There are conflicting reports about whether BMP signaling is required for eyelid closure during fetal development. This question was addressed using mice deficient in BMP or TGFbeta signaling in prospective eyelid and conjunctival epithelial cells. Genes encoding two type I BMP receptors, the type II TGFbeta receptor, two BMP- or two TGFbeta-activated R-Smads or the co-Smad Smad4 were deleted from the ocular surface ectoderm using Cre recombinase. Only mice with deletion of components of the BMP pathway had an 'eyelid open at birth' phenotype. Mice lacking Fgf10 or Fgfr2 also have open eyelids at birth. To better understand the pathways that regulate BMP expression and function during eyelid development, we localized BMPs and BMP signaling intermediates in Fgfr2 and Smad4 conditional knockout (CKO) mice. We found that Fgfr2 was required for the expression of Bmp4, the normal distribution of Shh signaling and for preserving the differentiation of the conjunctival epithelium. FGF signaling also promoted the expression of the Wnt antagonist Sfrp1 and suppressed Wnt signaling in the prospective eyelid epithelial cells, independently of BMP function. Transcripts encoding Foxc1 and Foxc2, which were previously shown to be necessary for eyelid closure, were not detectable in Smad4(CKO) animals. c-Jun, another key regulator of eyelid closure, was present and phosphorylated in eyelid periderm cells at the time of fusion, but failed to translocate to the nucleus in the absence of BMP function. Smad4(CKO) mice also showed premature differentiation of the conjunctival epithelium, conjunctival hyperplasia and the acquisition of epidermal characteristics, including formation of an ectopic row of hair follicles in place of the Meibomian glands. A second row of eyelashes is a feature of human lymphedema-distichiasis syndrome, which is associated with mutations in FOXC2.
PMID: 19369394
