Talk:Integumentary System Development
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Cite this page: Hill, M.A. (2026, March 6) Embryology Integumentary System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Integumentary_System_Development |
10 Most Recent Papers
Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)
Integument Development
<pubmed limit=5>Integument Development</pubmed>
2014
Wnt11 is required for oriented migration of dermogenic progenitor cells from the dorsomedial lip of the avian dermomyotome
PLoS One. 2014 Mar 26;9(3):e92679. doi: 10.1371/journal.pone.0092679. eCollection 2014.
Morosan-Puopolo G1, Balakrishnan-Renuka A1, Yusuf F2, Chen J2, Dai F3, Zoidl G2, Lüdtke TH4, Kispert A4, Theiss C2, Abdelsabour-Khalaf M5, Brand-Saberi B6. Author information
Abstract The embryonic origin of the dermis in vertebrates can be traced back to the dermomyotome of the somites, the lateral plate mesoderm and the neural crest. The dermal precursors directly overlying the neural tube display a unique dense arrangement and are the first to induce skin appendage formation in vertebrate embryos. These dermal precursor cells have been shown to derive from the dorsomedial lip of the dermomyotome (DML). Based on its expression pattern in the DML, Wnt11 is a candidate regulator of dorsal dermis formation. Using EGFP-based cell labelling and time-lapse imaging, we show that the Wnt11 expressing DML is the source of the dense dorsal dermis. Loss-of-function studies in chicken embryos show that Wnt11 is indeed essential for the formation of dense dermis competent to support cutaneous appendage formation. Our findings show that dermogenic progenitors cannot leave the DML to form dense dorsal dermis following Wnt11 silencing. No alterations were noticeable in the patterning or in the epithelial state of the dermomyotome including the DML. Furthermore, we show that Wnt11 expression is regulated in a manner similar to the previously described early dermal marker cDermo-1. The analysis of Wnt11 mutant mice exhibits an underdeveloped dorsal dermis and strongly supports our gene silencing data in chicken embryos. We conclude that Wnt11 is required for dense dermis and subsequent cutaneous appendage formation, by influencing the cell fate decision of the cells in the DML.
PMID 24671096
2013
2011
Neonatal skin maturation--vernix caseosa and free amino acids
Pediatr Dermatol. 2011 Mar-Apr;28(2):122-32. doi: 10.1111/j.1525-1470.2011.01309.x.
Visscher MO, Utturkar R, Pickens WL, LaRuffa AA, Robinson M, Wickett RR, Narendran V, Hoath SB. Source The Skin Sciences Institute, Division of Neonatology and Pulmonary Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. Marty.Visscher@cchmc.org
Abstract
Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with vernix caseosa retained is more hydrated than skin with vernix removed. This study examines the potential roles of free amino acids and vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after vernix caseosa retention or removal and compared to neonatal foreskin, vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with vernix caseosa removed, and it paralleled the higher stratum corneum hydration of vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in vernix caseosa-retained skin appear to originate from vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices.
© 2011 Wiley Periodicals, Inc.
PMID 21504444
2010
Role of canonical Wnt signaling/ß-catenin via Dermo1 in cranial dermal cell development
Development. 2010 Dec;137(23):3973-84. Epub 2010 Oct 27.
Tran TH, Jarrell A, Zentner GE, Welsh A, Brownell I, Scacheri PC, Atit R.
Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA. Abstract Cranial dermis develops from cephalic mesoderm and neural crest cells, but what signal(s) specifies the dermal lineage is unclear. Using genetic tools to fate map and manipulate a cranial mesenchymal progenitor population in the supraorbital region, we show that the dermal progenitor cells beneath the surface ectoderm process canonical Wnt signaling at the time of specification. We show that Wnt signaling/β-catenin is absolutely required and sufficient for Dermo1 expression and dermal cell identity in the cranium. The absence of the Wnt signaling cue leads to formation of cartilage in craniofacial and ventral trunk regions at the expense of dermal and bone lineages. Dermo1 can be a direct transcription target and may mediate the functional role of Wnt signaling in dermal precursors. This study reveals a lineage-specific role of canonical Wnt signaling/β-catenin in promoting dermal cell fate in distinct precursor populations.
PMID: 20980404
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.
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
2009
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
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
2008
Unraveling the mystery of vernix caseosa
Indian J Dermatol. 2008;53(2):54-60.
Singh G, Archana G. Source 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
1991
Integrin expression during human epidermal development in vivo and in vitro
Development. 1991 May;112(1):193-206.
Hertle MD, Adams JC, Watt FM. Source Keratinocyte Laboratory, Imperial Cancer Research Fund, London, UK. Abstract In order to investigate the role of extracellular matrix receptors of the integrin family in establishing the spatial organization of epidermal kerotinocytes, we used immunofluorescence microscopy to examine the expression of a range of integrin subunits during development of human palm and sole skin. All of the integrins expressed during development were also present in mature epidermis and were largely confined to the basal layer of keratinocytes in a pericellular distribution. The alpha 3 and beta 1 subunits were expressed prior to the initiation of stratification and did not change in abundance or distribution during subsequent development. alpha 4 and beta 3 were not detected at any time in the epidermis. Every other subunit examined showed spatial or temporal changes in expression. Staining for alpha 1 was strong before stratification and until mid-development, but was greatly decreased in neonatal epidermis. alpha 2 was first detected in small patches of basal cells prior to stratification, and thereafter was found in the entire basal layer, with greater staining in developing sweat glands. alpha 5 was not expressed until mid-development, and then primarily in developing sweat glands, with faint expression in neonatal epidermis. alpha v was detected following stratification, in developing sweat glands, and occasionally in neonatal epidermis. alpha 6 and beta 4 were peribasally expressed before stratification, but thereafter became concentrated at the basal cell surface in contact with the basement membrane, co-localizing with hemidesmosomes as determined by staining with bullous pemphigoid antiserum. We also examined the distribution of three known ligands for keratinocyte integrins: laminin and collagen type IV were present in the basement membrane zone at all stages of development, whereas fibronectin was only evident there until about 13 weeks estimated gestational age. Finally, we found that the changes in integrin expression that occur on initiation of stratification in vivo could be reproduced in organ cultures of developing skin; such cultures therefore provided a useful experimental model for further studies of the role of integrins in epidermal stratification.
PMID 1769328
Biology and Genetics of Hair. http://www.ncbi.nlm.nih.gov/pubmed/20590427
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064709/?tool=pubmed
Sensory
Transient receptor potential channel - (TRP) a transmembrane protein acting as a thermo-sensitive channel that is expressed on sensory neurons and skin epithelial cells in vertebrate and non-vertebrate animals. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662787
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
AP-2 factors act in concert with Notch to orchestrate terminal differentiation in skin epidermis
J Cell Biol. 2008 Oct 6;183(1):37-48. Epub 2008 Sep 29.
Wang X, Pasolli HA, Williams T, Fuchs E.
The Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA. Abstract The mechanisms by which mammalian epidermal stem cells cease to proliferate and embark upon terminal differentiation are still poorly understood. By conditionally ablating two highly expressed transcription factors, AP-2alpha and AP-2gamma, we unmasked functional redundancies and discovered an essential role for AP-2s in the process. In vivo and in vitro, AP-2 deficiency is accompanied by surprisingly minimal changes in basal gene expression but severely perturbed terminal differentiation and suppression of additional transcription factors and structural genes involved. In dissecting the underlying molecular pathways, we uncover parallel pathways involving AP-2 and Notch signaling, which converge to govern CCAAT/enhancer binding protein genes and orchestrate the transition from basal proliferation to suprabasal differentiation. Finally, we extend the striking similarities in compromising either Notch signaling or AP-2alpha/AP-2gamma in developing skin to that in postnatal skin, where all hair follicles and sebaceous gland differentiation are also repressed and overt signs of premalignant conversion emerge.
PMID: 18824566
