The ciliopathy gene Rpgrip1l is essential for hair follicle development.
The ciliopathy gene Rpgrip1l is essential for hair follicle development.
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DOI：
10.1038/jid.2014.483
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发表时间：
2015-03
影响因子：
6.5
通讯作者：
Clark, Richard A.
中科院分区：
文献类型：
--
作者：
Chen, Jiang;Laclef, Christine;Moncayo, Alejandra;Snedecor, Elizabeth R.;Yang, Ning;Li, Li;Takemaru, Ken-Ichi;Paus, Ralf;Schneider-Maunoury, Sylvie;Clark, Richard A.
初级纤毛通过调节Notch、Wnt和hedgehog信号通路对皮肤形态发生至关重要。先前对皮肤中初级纤毛功能的研究是基于对纤毛形成所必需的基因的研究。然而，这些纤毛基因中没有一个与纤毛病有关，纤毛病是一组由纤毛异常形成或功能引起的疾病。为了确定纤毛病变和皮肤形态发生之间是否存在遗传和分子联系，我们研究了RPGRIP1L在皮肤发育中的作用，RPGRIP1L是Joubert（JBTS）和Meckel（MKS）综合征（两种严重形式的纤毛病变）中突变的基因。我们发现RPGRIP1L是毛囊形态发生所必需的。具体来说，破坏小鼠的Rpgril1基因导致毛囊角质形成细胞的增殖和分化减少，导致毛囊发育缺陷。这些缺陷与初级纤毛形成显著减少和减弱的hedgehog信号传导相关。相反，我们发现毛囊诱导和极化以及毛囊间表皮的发育不受影响。这项研究表明，RPGRIP1L，一个纤毛病基因，是毛囊形态发生所必需的，可能通过调节初级纤毛的形成和刺猬信号通路。
The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia. To determine whether there is a genetic and molecular link between ciliopathies and skin morphogenesis, we investigated the role of RPGRIP1L, a gene mutated in Joubert (JBTS) and Meckel (MKS) syndromes, two severe forms of ciliopathy, in the context of skin development. We found that RPGRIP1L is essential for hair follicle morphogenesis. Specifically, disrupting the Rpgril1 gene in mice resulted in reduced proliferation and differentiation of follicular keratinocytes, leading to hair follicle developmental defects. These defects were associated with significantly decreased primary cilium formation and attenuated hedgehog signaling. In contrast, we found that hair follicle induction and polarization and the development of interfollicular epidermis were unaffected. This study indicates that RPGRIP1L, a ciliopathy gene, is essential for hair follicle morphogenesis likely through regulating primary cilia formation and the hedgehog signaling pathway.
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DOI：
10.1038/jid.2008.279
发表时间：
2009-02
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.8
作者：
Bershteyn, Marina;Atwood, Scott X.;Woo, Wei-Meng;Li, Mischa;Oro, Anthony E.
通讯作者：
Oro, Anthony E.
影响因子：
2.7
作者：
Chiang, C;Swan, RZ;Dlugosz, AA
通讯作者：
Dlugosz, AA
影响因子：
4.6
作者：
Croyle, Mandy J.;Lehman, Jonathan M.;Yoder, Bradley K.
通讯作者：
Yoder, Bradley K.
DOI：
10.1073/pnas.0402802101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Guo, N;Hawkins, C;Nathans, J
通讯作者：
Nathans, J