Abstract
Organ morphogenesis is a complex process coordinated by cell specification, epithelial-mesenchymal interactions and tissue polarity. A striking example is the pattern of regularly spaced, globally aligned mammalian hair follicles, which emerges through epidermal-dermal signaling and planar polarized morphogenesis. Here, using live-imaging, we discover that developing hair follicles polarize through dramatic cell rearrangements organized in a counter-rotational pattern of cell flows. Upon hair placode induction, Shh signaling specifies a radial pattern of progenitor fates that, together with planar cell polarity, induce counter-rotational rearrangements through myosin and ROCK-dependent polarized neighbour exchanges. Importantly, these cell rearrangements also establish cell fate asymmetry by repositioning radial progenitors along the anterior-posterior axis. These movements concurrently displace associated mesenchymal cells, which then signal asymmetrically to maintain polarized cell fates. Our results demonstrate how spatial patterning and tissue polarity generate an unexpected collective cell behaviour that in turn, establishes both morphological and cell fate asymmetry.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 541-552 |
| Number of pages | 12 |
| Journal | Nature Cell Biology |
| Volume | 20 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2018 |
| Externally published | Yes |
Bibliographical note
Funding Information:We gratefully acknowledge those who provide mouse lines, technical support, and valuable discussions that contributed to this project. We thank Saori Haigo and Jeremy Reiter for generous donation of Vangl2 and Fz6 alleles in mT/mG backgrounds. Michael Deans and Jeremy Nathans kindly provided the Vangl2 and Vangl1 floxed mouse lines. Beniot Aiguoy developed and distributed Packing Analyzer v2 and Tissue Analyzer software for image analysis. We thank Katie Little for assistance with genetic crosses and genotyping, and members of the Devenport lab for insightful comments and suggestions. Finally, we thank Gary Laevsky for imaging support and expertise. The Confocal Facility at Princeton University is a Nikon Center of Excellence. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01AR066070 and a Vallee Foundation Scholars Award to D.D. L.L. was supported by NIH training grant T32 GM007388.
Publisher Copyright:
© 2018 The Author(s).