Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis.
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-Jkappa 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.
Hu
Bing
B
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Lefort
Karine
K
Qiu
Wenying
W
Nguyen
Bach-Cuc
BC
Rajaram
Renuga Devi
RD
Castillo
Einar
E
He
Fenglei
F
Chen
Yiping
Y
Angel
Peter
P
Brisken
Cathrin
C
Dotto
G Paolo
GP
D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017353:Gene Deletion; D018859:Hair Follicle; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
D051858:Forkhead Transcription Factors; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; C090140:Whn protein; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse