Estrach Soline, Ambler Carrie A, Lo Celso Cristina, Hozumi Katsuto, Watt Fiona M
Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Development. 2006 Nov;133(22):4427-38. doi: 10.1242/dev.02644. Epub 2006 Oct 11.
The Wnt and Notch signalling pathways regulate hair follicle maintenance, but how they intersect is unknown. We show that Notch signalling is active in the hair follicle pre-cortex, a region of high Wnt activity, where commitment to hair lineages occurs. Deletion of jagged 1 (Jag1) results in inhibition of the hair growth cycle and conversion of hair follicles into cysts of cells undergoing interfollicular epidermal differentiation. Conversely, activation of Notch in adult epidermis triggers expansion of the base of the hair follicle, sebaceous gland enlargement and abnormal clumping of the follicles. In adult epidermis, the induction of new hair follicle formation by beta-catenin is prevented by blocking Notch signalling pharmacologically or through Jag1 deletion. Conversely, activation of both pathways accelerates growth and differentiation of ectopic follicles. beta-catenin stimulates Notch signalling by inducing Jag1 transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta-catenin pathway to determine epidermal cell fate.
Wnt和Notch信号通路调控毛囊的维持，但它们如何相互作用尚不清楚。我们发现Notch信号在毛囊前皮质中活跃，该区域Wnt活性较高，毛囊谱系的定向分化在此发生。锯齿状蛋白1（Jag1）的缺失导致毛发生长周期受到抑制，毛囊转变为经历毛囊间表皮分化的细胞囊肿。相反，在成年表皮中激活Notch会引发毛囊底部扩张、皮脂腺增大以及毛囊异常聚集。在成年表皮中，通过药理学方法阻断Notch信号或通过缺失Jag1可阻止β-连环蛋白诱导新毛囊形成。相反，两条信号通路的激活均会加速异位毛囊的生长和分化。β-连环蛋白通过诱导Jag1转录来刺激Notch信号。我们得出结论，Notch信号通路在Wnt/β-连环蛋白信号通路的下游起作用，以决定表皮细胞的命运。
