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神经嵴干细胞特异性敲除 Pygopus2 基因可调节毛囊发育。

Neural crest stem cell-specific deletion of the Pygopus2 gene modulates hair follicle development.

机构信息

Institute of Genetic Medicine, Newcastle University, Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.

出版信息

Stem Cell Rev Rep. 2014 Feb;10(1):60-8. doi: 10.1007/s12015-013-9466-z.

DOI:10.1007/s12015-013-9466-z
PMID:23955574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3907677/
Abstract

We show that neural crest stem cells affect mouse hair follicle development. During embryogenesis hair follicle induction is regulated by complex reciprocal and functionally redundant signals between epidermis and dermis, which remain to be fully understood. Canonical Wnt signalling is a hallmark of neural crest cells and also a prerequisite for hair follicle induction prior to hair placode formation in the epidermis. As neural crest stem cells invade the epidermis during early embryonic development we aimed at determining whether neural crest cells affect hair follicle development. To attenuate, but not silence, canonical Wnt signalling specifically in neural crest cells, we analyzed Wnt1-cre(+/-)::Pygo2(-/-) mice in which the β-catenin co-activator gene, Pygopus 2 (Pygo2), is deleted specifically in neural crest cells. Both, hair density and hair thickness were reduced in mutant mice. Furthermore, hair development was delayed and the relative ratio of hair types was affected. There was a decrease in zig-zag hairs and an increase in awl hairs. Mouse neural crest stem cells expressed ectodysplasin, an essential effector in the formation of zig-zag hair. Taken together, our data support the novel notion that neural crest cells are involved in the earliest stages of hair follicle development.

摘要

我们证明神经嵴干细胞会影响小鼠毛囊的发育。在胚胎发生过程中,毛囊的诱导受到表皮和真皮之间复杂的相互和功能冗余信号的调节,这些信号仍有待充分理解。经典 Wnt 信号是神经嵴细胞的标志,也是表皮毛盘形成之前诱导毛囊形成的必要条件。由于神经嵴干细胞在胚胎早期侵入表皮,我们旨在确定神经嵴细胞是否会影响毛囊的发育。为了特异性地减弱而非沉默神经嵴细胞中的经典 Wnt 信号,我们分析了 Wnt1-cre(+/-)::Pygo2(-/-) 小鼠,其中β-连环蛋白共激活基因 Pygopus 2 (Pygo2)特异性地在神经嵴细胞中缺失。突变小鼠的毛发密度和毛发厚度都降低了。此外,毛发发育延迟,毛发类型的相对比例受到影响。Zigzag 毛发减少,awl 毛发增加。小鼠神经嵴干细胞表达外胚层蛋白,这是 zigzag 毛发形成的必需效应物。总之,我们的数据支持了一个新的观点,即神经嵴细胞参与了毛囊发育的最早阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/45d70522d1a6/12015_2013_9466_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/a8b639b2adc8/12015_2013_9466_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/2a51919fc40a/12015_2013_9466_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/3915b3cb24d5/12015_2013_9466_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/3dbd136ef635/12015_2013_9466_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/1f1d967d737c/12015_2013_9466_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/45d70522d1a6/12015_2013_9466_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/a8b639b2adc8/12015_2013_9466_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/2a51919fc40a/12015_2013_9466_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/3915b3cb24d5/12015_2013_9466_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/3dbd136ef635/12015_2013_9466_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/1f1d967d737c/12015_2013_9466_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3647/3907677/45d70522d1a6/12015_2013_9466_Fig6_HTML.jpg

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J Invest Dermatol. 2013 Apr;133(4):890-8. doi: 10.1038/jid.2012.407. Epub 2012 Nov 29.
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Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation.
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