Abstract
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.
Highlights
The mesenchymal condensation, first recognized in limb bud condensations and named ‘precartilage condensates’ by Dame Honor Fell (Fell, 1925), is a tissue-level structure preceding organ development
Dermal fibroblasts condense and change shape below the developing hair follicle placode To determine to what extent the fibroblasts within the dermal condensate are more densely packed than the interfollicular fibroblasts, we examined primary HFs in E14.5 whole skin in 3D using confocal microscopy
We have previously shown that Fgf20b-Gal/b-Gal mice lack all molecular signs of primary dermal condensates (DC) formation including Sox2 (Huh et al, 2013) (Figure 1A, right panel), and quantification of dermal fibroblast density directly underneath the Fibroblast Growth Factor 20 (Fgf20)-/- placode revealed that these fibroblasts exhibit density similar to that of the wild-type interfollicular dermis (p=0.962425) (Figure 1B)
Summary
The mesenchymal condensation, first recognized in limb bud condensations and named ‘precartilage condensates’ by Dame Honor Fell (Fell, 1925), is a tissue-level structure preceding organ development. Condensations are morphologically distinguishable and are defined as a local increase in cell density. Characteristics of condensing mesenchymal cells include a change in cell shape, close surface contact between adjacent cells, and increased nucleus-to-cytoplasm ratio (Thorogood and Hinchliffe, 1975; Searls et al, 1972) (for review see [Hall and Miyake, 2000]). The question of how a local increase in cell density is achieved remains to be addressed. Several modes of cell condensation have been proposed, including i) increase in mitotic activity, ii) active migration of cells, and iii) failure of cells to disperse due to changes in cell-cell and/or cell-extracellular matrix (ECM) interactions (Hall and Miyake, 1992)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
