Jagged 1 is a β-catenin target gene required for ectopic hair follicle formation in adult epidermis

Author:

Estrach Soline1,Ambler Carrie A.1,Lo Celso Cristina Lo1,Hozumi Katsuto2,Watt Fiona M.1

Affiliation:

1. Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

2. Department of Immunology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Abstract

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 β-catenin is prevented by blocking Notch signalling pharmacologically or through Jag1 deletion. Conversely, activation of both pathways accelerates growth and differentiation of ectopic follicles.β-catenin stimulates Notch signalling by inducing Jag1transcription. We conclude that the Notch pathway acts downstream of the Wnt/β-catenin pathway to determine epidermal cell fate.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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