title: Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a.
abstract: The pharyngeal pouches are a segmental series of epithelial structures that organize the embryonic vertebrate face. In mice and zebrafish that carry mutations in homologs of the DiGeorge syndrome gene TBX1, a lack of pouches correlates with severe craniofacial defects, yet how Tbx1 controls pouch development remains unclear. Using mutant and transgenic rescue experiments in zebrafish, we show that Tbx1 functions in the mesoderm to promote the morphogenesis of pouch-forming endoderm through wnt11r and fgf8a expression. Consistently, compound losses of wnt11r and fgf8a phenocopy tbx1 mutant pouch defects, and mesoderm-specific restoration of Wnt11r and Fgf8a rescues tbx1 mutant pouches. Time-lapse imaging further reveals that Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells. We therefore propose a two-step model in which Tbx1 coordinates the Wnt-dependent epithelial destabilization of pouch-forming cells with their collective migration towards Fgf8a-expressing mesodermal guideposts.
authors.affiliation: Broad California Institute of Regenerative Medicine Center, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Chong Pyo
authors.initials: CP
authors.lastname: Choe
authors.affiliation: Broad California Institute of Regenerative Medicine Center, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA gcrump@usc.edu.
authors.forename: J Gage
authors.initials: JG
authors.lastname: Crump
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004848:Epithelium / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D038081:Organogenesis / Q000502:physiology*; D010614:Pharynx / Q000196:embryology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D059008:Time-Lapse Imaging; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020825:T-Box Domain Proteins; C000592648:Tbx1 protein, zebrafish; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; C517774:fgf8a protein, zebrafish; D005346:Fibroblast Growth Factors
keywords: Epithelial morphogenesis; Fgf8; Pharyngeal pouches; Tbx1; Wnt11r; Zebrafish