Dchs1-Fat4 regulation of polarized cell behaviours during skeletal morphogenesis.

Yaopan Mao,Joanna Mulvaney,Danielle Whiting,Tina Martin,Anna Kuta,Ivan Crespo-Enriquez,Philippa Francis-West,Kenneth D Irvine

doi:10.1038/ncomms11469

Abstract

Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown. An example of extreme diversity in the shape of a skeletal structure can be seen in the sternum, which varies considerably across species. Here we show that the Dchs1–Fat4 planar cell polarity pathway controls cell orientation in the early skeletal condensation to define the shape and relative dimensions of the mouse sternum. These changes fit a model of cell intercalation along differential Dchs1–Fat4 activity that drives a simultaneous narrowing, thickening and elongation of the sternum. Our results identify the regulation of cellular polarity within the early pre-chondrogenic mesenchyme, when skeletal shape is established, and provide the first demonstration that Fat4 and Dchs1 establish polarized cell behaviour intrinsically within the mesenchyme. Our data also reveal the first indication that cell intercalation processes occur during ventral body wall elongation and closure.

Highlights

Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown
While there are many examples of cellular polarization in vertebrates controlled by Fz–Vang Planar cell polarity (PCP) in both the epithelium and mesenchyme, only two clear examples of cellular polarization directed by Ds–Fat PCP in vertebrates have been identified: Dchs1–Fat[4] regulate the orientation of cell divisions within the kidney tubule epithelium and the collective migration of facial branchiomotor neurons within the hindbrain[3,4]
Here we have identified a new role for Dchs1–Fat[4] PCP in vertebrates by establishing that Dchs1–Fat[4] control cell orientation within the sternal mesenchyme to determine its final shape

Summary

Introduction

Skeletal shape varies widely across species as adaptation to specialized modes of feeding and locomotion, but how skeletal shape is established is unknown. We show that the Dchs1–Fat[4] planar cell polarity pathway controls cell orientation in the early skeletal condensation to define the shape and relative dimensions of the mouse sternum. These changes fit a model of cell intercalation along differential Dchs1–Fat[4] activity that drives a simultaneous narrowing, thickening and elongation of the sternum. Mice mutant for Fat[4] or Dchs[1] are characterized by a wide range of defects in organogenesis, but in general, the underlying mechanisms that cause these defects are unknown[3,5] These abnormalities include changes in the development of the sternum and vertebrae that are endochondral bones forming via a cartilage intermediate.

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