The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation.
The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation.
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DOI：
10.1038/jid.2010.391
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发表时间：
2011-04
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影响因子：
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在Hox基因中，Hoxc13已被证明对正常的毛干分化至关重要，因为Hoxc13基因靶向（Hoxc13tm1Mrc）小鼠完全缺乏外毛。由于与Foxn1nu（裸）突变小鼠显着的显性表型相似，我们试图确定Hoxc13和Foxn1是否可能在毛囊（HF）分化的共同途径中起作用。我们发现Hoxc13tm1Mrc和Foxn1nu小鼠所表现出的脱发是由于毛干分化的惊人相似的缺陷，并且这两个突变体都患有严重的指甲营养不良。这些表型相似性与HF和甲基质中Hoxc13和Foxn1表达模式的广泛重叠一致。此外，对Hoxc13tm1Mrc小鼠皮肤的DNA微阵列分析发现，Foxn1与许多毛发角蛋白基因一起显著下调。我们通过共转染和染色质免疫沉淀（ChIP）实验获得的结果表明，Foxn1的下调显然反映了HOXC13直接转录控制的丧失。正如在讨论中提出的，这些数据支持角化细胞分化的调控模型，其中hoxc13依赖性Foxn1的激活是控制终端分化标记表达的调控级联的一部分。
Among the Hox genes, Hoxc13 has been shown to be essential for proper hair shaft differentiation as Hoxc13 gene-targeted (Hoxc13tm1Mrc) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1nu (nude) mutant mice, we sought to determine whether Hoxc13 and Foxn1 might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13tm1Mrc and Foxn1nu mice is due to strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13tm1Mrc mice identified Foxn1 as significantly down-regulated along with numerous hair keratin genes. This Foxn1 down-regulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers.
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影响因子：
2.9
作者：
Bazzi, Hisham;Demehri, Shadmehr;Potter, Christopher S.;Barber, Alison G.;Awgulewitsch, Alexander;Kopan, Raphael;Christiano, Angela M.
通讯作者：
Christiano, Angela M.
影响因子：
4.8
作者：
Jave-Suarez, LF;Winter, H;Schweizer, J
通讯作者：
Schweizer, J
影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
64.5
作者：
Kljuic, A;Bazzi, H;Christiano, AM
通讯作者：
Christiano, AM
DOI：
10.1038/sj.jidsp.5640235
发表时间：
1999-12-01
影响因子：
--
作者：
Chuong, CM;Noveen, A
通讯作者：
Noveen, A