|Title:||The function of Twist1 in the Cranial Mesoderm|
|Publisher:||University of Sydney.|
The Faculty of Medicine.
Children's Medical Research Institute.
Children's Hospital at Westmead Clinical School.
|Abstract:||The transcription factor Twist1 is a key regulator of craniofacial development. Deletion of Twist1 in the mouse embryo leads to neural tube defects, abnormal head development and mid-gestational lethality. To dissect the function of Twist1 in the cranial mesoderm (CM) beyond mid-gestation, the Mesp1-Cre transgenic line was used to delete Twist1 in the anterior mesoderm, including the progenitors of the CM. Loss of Twist1 in CM cells resulted in loss and malformations of the cranial mesoderm-derived skeleton and failure to fully segregate the mesoderm and the neural crest cells. The development of extraocular muscles was compromised whereas the differentiation of branchial arch muscles was not affected, indicating a differential requirement for Twist1 in these two types of craniofacial muscle. Surprisingly, loss of Twist1 led to the inability of the mesodermal cells to maintain their mesenchymal characteristics followed by acquisition of an epithelial-like morphology. Microarray analysis of the Twist1 deficient embryos revealed gene expression changes relating to cell–matrix interaction, blood vessel morphogenesis and regulation of Epithelial to Mesenchymal Transition (EMT). Combining the microarray data set with ChIP-sequencing identified Prrx1 and Ddr2at least two Twist1 transcriptional targets Prrx1 and Ddr2, both involved in EMT and the propagation of the mesenchymal cell characteristics. The findings presented in this thesis point to a central role of role of Twist1 in maintaining the mesenchymal architecture and the progenitor state of the mesoderm necessary for proper craniofacial development.|
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|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|BILDSOE Heidi - Final thesis.pdf||Thesis||24.23 MB||Adobe PDF|