eLife · 2018 · 100 citations · 81 references
Life SciencesCell BiologyDevelopmental BiologyMorphogenesisOrganogenesisTissue DifferentiationCell Fate DeterminationCell MigrationDevelopmental Cell SignalingMesenchymal MorphogenesisMorphogenetic Cell BehaviorsCell Motility AnalysisCell Motility ModulationDermal MorphogenesisDevelopmental Cell Cycle ExitHair Cycle RegulationHair Follicle AnatomyHair Follicle Differentiation
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.
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