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Нair Growth Disorders Caused by Mutant Genes hr, we, wal and Fgf5go-Y in Mice are Associated with Disruption of BMP and WNT Pathways in Skin
Poster Title: Нair Growth Disorders Caused by Mutant Genes hr, we, wal and Fgf5go-Y in Mice are Associated with Disruption of BMP and WNT Pathways in Skin
Submitted on 21 Feb 2017
Author(s): Anastasia P. Nesterova, Pavel K. Golovatenko-Abramov, Eugene S. Platonov
Affiliations: Laboratory of Developmental Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences
This poster was presented at BIT Life Sciences’ 3rd Annual World Congress of Gene, 1-7 December, Foshan, China
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Poster Information
Abstract: Introduction:
Morphogenetic cycle of hair follicle in mammalians is sophisticated self-regulated system that is controlled by coordinated activity of diverse signaling pathways and gene regulatory networks. Determining gene networks necessary for initiation and termination cyclic hair development is key task in this area of research. Ability of direct enhancement or suppression of hair growth depends on the solution of this task. Mutant alleles that cause various alterations in hair coat formation in mices are convenient tool for exploring activity of gene regulatory networks.
Hair cycle stages within 1st and 2nd hair generation in mice were determined using histological approaches. Expression of BMP-dependent genes Bmp2, Id1, Sostdc1 and WNT-dependent gene Mitf in probes of skin of mice of various genotypes was evaluated using qRT-PCR approach (SYBR Green I/ROX staining, iCycler iQ machine, Bio-Rad). Pathway analysis was performed using ResNet Mammalian Database and Pathway Studio application (Ariadne Genomics Inc.)
In skin of C57Bl6 wild-type mice, elevation of BMP-dependent Sostdc1 gene mRNA expression entailed downregulation of WNT-dependent Mitf gene mRNA expression. In skin of Hrhr/Hrhr mutant mice, elevation of Sostdc1 mRNA expression is not associated with downregulation of WNT-dependent gene network. In skin of wild-type mice, BMP gene network retains high activity level at the end of catagen/beginning of telogen stage, and in the middle of anagen stage of hair cycle. In mutant we/we wal/wal mice, expression of BMP-associated Bmp2 and Id1 genes was increased, as compared to wild-type mice probes. Mutant Fgf5go-Y gene partially normalizes BMP gene network activity in Fgf5go-Y/Fgf5go-Y we/we wal/wal genotype mice.
It is shown for the first time that beginning of anagen, catagen and telogen stages of hair cycle correlates with changes in transcriptional activity of Bmp2 and Id1 genes in skin of wild-type mice. Upregulation of BMP gene network leads to alterations of cyclic hair growth and progression of alopecia. Inhibition of WNT-dependent gene network by activity of BMP gene network is required for anagen-to-catagen switch.
Summary: The aim of present study was to analyze changes in expression of BMP- and WNT-dependent genetic markers during hair cycle in skin of homozygotous mice carrying mutant alleles of angora (Fgf5go-Y), hairless (Hrhr), waved alopecia (wal) and wellhaarig (we) genes in different combinations. Inhibition of MItf and activity of Bmp2 and Id1 are required for anagen-to-catagen switch of second generation of hair follicles of mutant and C57Bl6 mices.References: J Dermatol Sci. 2010 Dec;60(3):201-3. doi: 10.1016/j.jdermsci.2010.10.002. Epub 2010 Nov 4.Report abuse »
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