Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis

被引：85

作者：

Hu, Bing ^{[1
]}

Lefort, Karine ^{[1
]}

Qiu, Wenying ^{[1
]}

Nguyen, Bach-Cuc ^{[2
]}

Rajaram, Renuga Devi ^{[3
]}

Castillo, Einar ^{[1
]}

He, Fenglei ^{[4
]}

Chen, Yiping ^{[4
]}

Angel, Peter ^{[5
]}

Brisken, Cathrin ^{[3
]}

Dotto, G. Paolo ^{[1
,2
]}

机构：

[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[2] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[3] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland

[4] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA

[5] German Canc Res Ctr, D-69120 Heidelberg, Germany

来源：

GENES & DEVELOPMENT | 2010年 / 24卷 / 14期

关键词：

Notch; Wnt; ROR2; FoxN1; epithelial-mesenchymal interactions; RECEPTOR TYROSINE KINASE; TERMINAL DIFFERENTIATION; TRANSCRIPTIONAL PROGRAM; C-JUN; NOTCH; GENE; EXPRESSION; WNT5A; PATHWAY; FOXN1;

D O I：

10.1101/gad.1886910

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-J kappa gene, the effector of "canonical'' Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch-CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.

引用

页码：1519 / 1532

页数：14

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