期刊
DEVELOPMENTAL BIOLOGY
卷 396, 期 1, 页码 1-7出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2014.09.029
关键词
Hedgehog; Wnt; Primary mouth; Xenopus; Mouse; Buccopharyngeal membrane; Stomodeum; Fibronectin
资金
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/E013872/1, BB/I021922/1]
- Wellcome Trust [081880/Z/06/Z]
- King's College London Dental studentship
- National Institute of Dental and Craniofacial Research/National Institutes of Health (NIDCR/NIH) [F32DE023272]
- National Institute of General Medical Sciences/National Heart, Lung and Blood Institute [GM074104, HL117164]
- Wellcome Trust [081880/Z/06/Z] Funding Source: Wellcome Trust
- BBSRC [BB/I021922/1, BB/E013872/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E013872/1, BB/I021922/1] Funding Source: researchfish
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. (C) 2014 Elsevier Inc. All rights reserved.
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