Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation

• Published in: eLife 2018-07, Vol.7
• Main Authors: Biggs, Leah C, Mäkelä, Otto Jm, Myllymäki, Satu-Marja, Das Roy, Rishi, Närhi, Katja, Pispa, Johanna, Mustonen, Tuija, Mikkola, Marja L
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Analysis; Animals; Cell Aggregation; Cell Biology; Cell Cycle; Cell Lineage; Cell Movement; Cell Shape; Criminal investigation; dermal condensate; Dermis - cytology; Dermis - ultrastructure; Developmental Biology; Embryo; Epithelium; Fgf20; Fibroblast Growth Factor 9 - pharmacology; Fibroblast growth factors; Fibroblast Growth Factors - metabolism; Fibroblasts - cytology; Fibroblasts - metabolism; Genes; hair follicle; Hair Follicle - cytology; live imaging; Mice, Inbred C57BL; Microscopy; Morphogenesis; Receptors, Fibroblast Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor - metabolism; RNA; RNA sequencing; RNAseq; Signal Transduction; Skin; SOXB1 Transcription Factors - metabolism; Stem cells; Transcription, Genetic; Travel
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.36468

Mesenchymal condensation is a critical step in organogenesis, yet the underlying molecular and cellular mechanisms remain poorly understood. The hair follicle dermal condensate is the precursor to the permanent mesenchymal unit of the hair follicle, the dermal papilla, which regulates hair cycling throughout life and bears hair inductive potential. Dermal condensate morphogenesis depends on epithelial Fibroblast Growth Factor 20 (Fgf20). Here, we combine mouse models with 3D and 4D microscopy to demonstrate that dermal condensates form de novo and via directional migration. We identify cell cycle exit and cell shape changes as early hallmarks of dermal condensate morphogenesis and find that Fgf20 primes these cellular behaviors and enhances cell motility and condensation. RNAseq profiling of immediate Fgf20 targets revealed induction of a subset of dermal condensate marker genes. Collectively, these data indicate that dermal condensation occurs via directed cell movement and that Fgf20 orchestrates the early cellular and molecular events.