The secondary mouth and its associated face and jaws were an important evolutionary adaptation in the vertebrate lineage. The secondary mouth is formed from facial prominences including the fronto-nasal prominence and the 1st pharyngeal-arch derived maxillary and mandibular prominence. Cranial neural crest cells within these prominences give rise to the connective tissues of face and jaws, and strict spatio-temporal regulation of cranial neural crest cell fate patterning and subsequent prominence outgrowth is vital to normal facial development. Oral-facial clefting (OFC) is a common morbid human birth disorder characterized by disrupted oral and craniofacial morphogenesis. Our previous studies demonstrate that a secreted signaling molecule, wnt9b, is required for both patterning of cranial neural crest cells and anterior-medial outgrowth of facial prominences in zebrafish. Importantly, WNT9B is associated with non-syndromic OFC in humans and Wnt9b loss-of-function in mice causes OFC. These lines of evidence strongly suggest a conserved role for Wnt9b during vertebrate secondary mouth formation, and suggest that zebrafish are an appropriate model to understand Wnt9b signaling architecture and its relation to OFC pathoetiology. Adding to our previous studies, we generated three novel wnt9b mutant zebrafish lines using CRISPR/Cas9 genome editing technology. Initial analysis of these mutant lines suggests that the N-terminal 136 amino acids of the zebrafish Wnt9b protein is sufficient for craniofacial development. Moreover, our data suggest the C-terminal portion of the zebrafish Wnt9b protein is not critical for wnt9b's role in craniofacial development. Further experiments are required to confirm our initial dataset and to explain how these different Wnt9b mutant proteins are capable of sustaining normal facial development. Taken together, these results provide crucial information to help elucidate wnt9b's influence upon development and disease pathogenesis.
|Advisor:||Jezewski, Peter, Javed, Amjad|
|Commitee:||Chang, Chenbei, MacDougall, Mary, Murphy-Ullrich, Joanne, Wang, Jianbo|
|School:||The University of Alabama at Birmingham|
|Department:||Joint Health Sciences|
|School Location:||United States -- Alabama|
|Source:||DAI-B 76/09(E), Dissertation Abstracts International|
|Subjects:||Genetics, Evolution and Development, Developmental biology|
|Keywords:||Cranial neural crest cells, Morphogenesis, Oral facial cleft, Patterning, Primary mouth, Secondary mouth|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be