title: Hedgehog activity controls opening of the primary mouth.
abstract: To feed or breathe, the oral opening must connect with the gut. The foregut and oral tissues converge at the primary mouth, forming the buccopharyngeal membrane (BPM), a bilayer epithelium. Failure to form the opening between gut and mouth has significant ramifications, and many craniofacial disorders have been associated with defects in this process. Oral perforation is characterized by dissolution of the BPM, but little is known about this process. In humans, failure to form a continuous mouth opening is associated with mutations in Hedgehog (Hh) pathway members; however, the role of Hh in primary mouth development is untested. Here, we show, using Xenopus, that Hh signaling is necessary and sufficient to initiate mouth formation, and that Hh activation is required in a dose-dependent fashion to determine the size of the mouth. This activity lies upstream of the previously demonstrated role for Wnt signal inhibition in oral perforation. We then turn to mouse mutants to establish that SHH and Gli3 are indeed necessary for mammalian mouth development. Our data suggest that Hh-mediated BPM persistence may underlie oral defects in human craniofacial syndromes.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King׳s College London, UK; Department of Molecular Biosciences, University of Texas at Austin, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Tabler
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King׳s College London, UK.
authors.forename: Trióna G
authors.initials: TG
authors.lastname: Bolger
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, USA; Howard Hughes Medical Institute, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wallingford
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King׳s College London, UK. Electronic address: karen.liu@kcl.ac.uk.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000196:embryology; D004848:Epithelium / Q000196:embryology; D005353:Fibronectins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D051379:Mice; D009025:Morpholines / Q000737:chemistry; D009055:Mouth / Q000196:embryology* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D011687:Purines / Q000737:chemistry; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis; D000074290:Zinc Finger Protein Gli3
chemical_list: D005353:Fibronectins; C108003:GLI3 protein, Xenopus; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009025:Morpholines; D009419:Nerve Tissue Proteins; D011687:Purines; D012097:Repressor Proteins; C558166:Shh protein, Xenopus; C465570:Shh protein, mouse; D051153:Wnt Proteins; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3; C470893:purmorphamine
keywords: Buccopharyngeal membrane; Fibronectin; Hedgehog; Mouse; Primary mouth; Stomodeum; Wnt; Xenopus