BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian Skin

• DOI: 10.1371/journal.pgen.1004687
• Publication Date: 2014-10-20T17:27:18Z
• Authors: Xiao-Jing Zhu; YuDong Liu; Zhong-Min Dai; Xiaoyun Zhang; XueQin Yang; Yan Li; Mengsheng Qiu; Jiang Fu; Wei Hsu; YiPing Chen; Zunyi Zhang
• Keywords: Keratinocytes; Smad5 Protein; Fibroblast Growth Factor 7; Mice, Transgenic; Bone Morphogenetic Protein 4; QH426-470; Receptors, G-Protein-Coupled; Smad1 Protein; 03 medical and health sciences; Genetics; Animals; Cell Proliferation; Skin; 0303 health sciences; Intracellular Signaling Peptides and Proteins; Gene Expression Regulation, Developmental; Phosphoproteins; Fibroblast Growth Factors; Epidermal Cells; Smad8 Protein; Bone Morphogenetic Proteins; Epidermis; Fibroblast Growth Factor 10; Research Article; Signal Transduction

Epidermal stratification of the mammalian skin requires proliferative basal progenitors to generate intermediate cells that separate from the basal layer and are replaced by post-mitotic cells. Although Wnt signaling has been implicated in this developmental process, the mechanism underlying Wnt-mediated regulation of basal progenitors remains elusive. Here we show that Wnt secreted from proliferative basal cells is not required for their differentiation. However, epidermal production of Wnts is essential for the formation of the spinous layer through modulation of a BMP-FGF signaling cascade in the dermis. The spinous layer defects caused by disruption of Wnt secretion can be restored by transgenically expressed Bmp4. Non-cell autonomous BMP4 promotes activation of FGF7 and FGF10 signaling, leading to an increase in proliferative basal cell population. Our findings identify an essential BMP-FGF signaling axis in the dermis that responds to the epidermal Wnts and feedbacks to regulate basal progenitors during epidermal stratification.