1362 The role of Fgf20 in establishing the hair follicle dermal condensate

Abstract

Hair follicle (HF) morphogenesis depends on reciprocal signalling between the epidermis and the underlying mesenchyme. The epithelial placode forms first and is accompanied by condensation of the adjacent dermis, known as the dermal condensate (DC). The DC is the precursor to the permanent, mesenchymal component of the HF, the dermal papilla (DP), which regulates the cycles of hair growth and rest throughout life, and is capable of generating a new hair follicle upon transplantation under epidermis. Thus, elucidation of the cellular and molecular mechanisms of DC development would be of great utility for regenerative purposes. Recently, our lab established the first molecular clue in DC development with the discovery that epithelial factor Fgf20 is necessary for DC induction. In the current study, we use a multifaceted approach including RNAseq and organ culture in combination with live tissue imaging to uncover the molecular and cellular responses to Fgf20 signalling as well as to determine the cellular events preceding and during DC development. We report that Fgf20 facilitates fibroblast migration and in short-term experiments can induce expression of some but not all DC markers. These cells, identified by Sox2 expression, do not arise from a predetermined population of Sox2+ cells. Further, as DC development progresses, these cells exit the cell cycle and migrate to form the DC. Additionally, DC cells adopt a convex shape early during HF morphogenesis, a phenotype that is recapitulated by local administration of FGF20 ex vivo, thus providing evidence that this is Fgf20-dependent. We show that modulation of FGF signalling during DC morphogenesis not only recapitulates the epidermal phenotype of Fgf20-/-, but it is also critical for DC cell attraction and maintenance. Together, these data suggest a role for Fgf20 in the cellular and molecular regulation of DC morphogenesis.