Talk:Integumentary System - Gland Development
Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development
Development. 2016 Dec 15;143(24):4723-4735. Epub 2016 Nov 18.
Sima J1, Piao Y2, Chen Y2, Schlessinger D1. Author information 1 Laboratory of Genetics and Genomics, NIA/NIH-IRP, 251 Bayview Blvd, room 10B014, Baltimore, MD 21224, USA email@example.com SchlessingerD@grc.nia.nih.gov. 2 Laboratory of Genetics and Genomics, NIA/NIH-IRP, 251 Bayview Blvd, room 10B014, Baltimore, MD 21224, USA. Abstract Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice. Consistent with transient Dkk4 action, intact Dkk4 inhibits MG extension but the cleaved form progressively increases during MG development with a concomitant upswing in Wnt activity. Furthermore, both Dkk4 and its receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction. In cell and organotypic cultures, Dkk4 inhibition is eliminated by elevation of Lrp6. Also, Lrp6 upregulation restores MG formation in Tabby mice. Thus, the dynamic state of Dkk4 itself and its interaction with Lrp6 modulates Wnt function during MG development, with a novel limitation of Dkk4 action by proteolytic cleavage. © 2016. Published by The Company of Biologists Ltd. KEYWORDS: Dkk4; Eda; Lrp6; Meibomian gland; Mouse; Proteolytic cleavage; Wnt PMID: 27864382 PMCID: PMC5201035 DOI: 10.1242/dev.143909
Involvement of Wnt, Eda and Shh at defined stages of sweat gland development
Development. 2014 Oct;141(19):3752-60. doi: 10.1242/dev.109231.
Cui CY1, Yin M2, Sima J2, Childress V2, Michel M2, Piao Y2, Schlessinger D2.
To maintain body temperature, sweat glands develop from embryonic ectoderm by a poorly defined mechanism. We demonstrate a temporal cascade of regulation during mouse sweat gland formation. Sweat gland induction failed completely when canonical Wnt signaling was blocked in skin epithelium, and was accompanied by sharp downregulation of downstream Wnt, Eda and Shh pathway genes. The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it is induced by Wnt/β-catenin; however, its overexpression repressed Wnt target genes and significantly reduced gland numbers. Eda signaling succeeded Wnt. Wnt signaling was still active and nascent sweat gland pre-germs were still seen in Eda-null mice, but the pre-germs failed to develop further and the downstream Shh pathway was not activated. When Wnt and Eda were intact but Shh was ablated, germ induction and subsequent duct formation occurred normally, but the final stage of secretory coil formation failed. Thus, sweat gland development shows a relay of regulatory steps initiated by Wnt/β-catenin - itself modulated by Dkk4 - with subsequent participation of Eda and Shh pathways. © 2014. Published by The Company of Biologists Ltd. KEYWORDS: Ectodermal dysplasia; Exocrine gland; Hair follicle; Heatstroke; Hyperhidrosis; Mouse; Skin appendage PMID 25249463 PMCID: PMC4197578 DOI: 10.1242/dev.109231
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. firstname.lastname@example.org 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
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
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.
Characterization of vernix caseosa: water content, morphology, and elemental analysis
J Invest Dermatol. 2000 Nov;115(5):875-81.
Pickens WL, Warner RR, Boissy YL, Boissy RE, Hoath SB.
The Skin Sciences Institute and Division of Neonatology, Children's Hospital Medical Center, Cincinnati, Ohio, USA. Abstract Recent studies have prompted interest in the use of epidermal barrier creams as protective biofilms for very low birthweight preterm infants. The key to understanding the role of epidermal barrier films is an elucidation of their interaction with water and a basic knowledge of their composition. In this study, we investigated the morphologic properties and elemental composition of the naturally occurring biofilm, vernix caseosa. This biofilm is typically lacking in preterm infants and its production coincides in utero with terminal differentiation of the epidermis and formation of the stratum corneum. Significantly, vernix (80.5+/-1.0% H2O) had a much higher water content than other barrier creams (Eucerin: 17.1+/-0.6%, Aquaphor: 0.33+/-0.03%, Ilex: 0.19+/-0.02%, petrolatum: 0.03+/-0.01%; all p<0.05). Phase contrast microscopy of vernix showed multiple cellular elements with nucleic "ghosts" embedded in a putative lipid matrix. Transmission electron microscopy revealed flattened structures approximately 1-2 microm in thickness with distinct cellular envelopes indicative of differentiated corneocytes. Compared with mature corneocytes in adult stratum corneum, vernix corneocytes appeared swollen, the density of the keratin filaments was less, and there was a relative lack of tonofilament orientation. Cryofractured specimens were examined by cryoscanning electron microscopy with subsequent elemental localization by X-ray beam analysis. The findings indicate the high water content of vernix is largely compartmentalized within fetal corneocytes. These results are consistent with the novel view of vernix as a "fluid phase" stratum corneum consisting of a hydrophobic lipid matrix with embedded fetal corneocytes possessing unique biomechanical and water-binding properties.
Branched chain fatty acids are constituents of the normal healthy newborn gastrointestinal tract
Pediatr Res. 2008 Dec;64(6):605-9.
Ran-Ressler RR, Devapatla S, Lawrence P, Brenna JT.
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA. Abstract Vernix suspended in amniotic fluid is normally swallowed by the late term fetus. We hypothesized that branched chain fatty acids (BCFA), long known to be major vernix components, would be found in meconium and that the profiles would differ systematically. Vernix and meconium were collected from term newborns and analyzed. BCFA-containing lipids constituted about 12% of vernix dry weight, and were predominantly saturated, and had 11-26 carbons per BCFA. In contrast, meconium BCFA had 16-26 carbons, and were about 1% of dry weight. Meconium BCFA were mostly in the iso-configuration, whereas vernix BCFA contained dimethyl and middle chain branching, and five anteiso-BCFA. The mass of BCFA entering the fetal gut as swallowed vernix particles is estimated to be 180 mg in the last month of gestation whereas the total mass of BCFA found in meconium is estimated to be 16 mg, thus most BCFA disappear from the fetal gut. The BCFA profiles of vernix and meconium show that BCFA are major components of normal healthy term newborn gastrointestinal tract. BCFA are candidates for agents that play a role in gut colonization and should be considered a nutritional component for the fetus/newborn.
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. email@example.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