title: Dchs1-Fat4 regulation of polarized cell behaviours during skeletal morphogenesis.
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.
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Yaopan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuta
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Crespo-Enriquez
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Whiting
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Martin
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mulvaney
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Irvine
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Philippa
authors.initials: P
authors.lastname: Francis-West
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000196:embryology* / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D008648:Mesoderm / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D015398:Signal Transduction; D013249:Sternum / Q000196:embryology / Q000378:metabolism
chemical_list: D015820:Cadherins; C506554:Dchs1 protein, mouse; C506555:Fat4 protein, mouse