The cranial skeleton develops as a result of the complex interaction of all three germs layers in a process that is largely conserved across vertebrates. Our current understanding of the genetic and developmental basis of the specification, growth, patterning, and morphogenesis required for propper Craniofacial development is insufficient to effectively identify, prevent, and treat human Craniofacial defects. While the roles of some genes involved in Craniofacial development have been illucidated, the roles of many other genes remain uncharacterized. One such gene is vgl-2a. We have demonstrated that reducing expression of vgl-2a in zebrafish results in a significant Craniofacial defect, illustrating an undescribed role for this gene in Craniofacial development. The objective of this proposal is to characterize this role. Specifically, I propose to determine the spatiotemporal pattern of expression of vgl-2a, identify the domain(s) of expression required for Craniofacial development, and identify the signal pathways and developmental processes vgl-2a participates in. Because of its homology to Vgl-2 in mouse, Vgl-2a is believed to act as a transcriptional cofactor and I intend to determine which transcription factor(s) it interacts with during Craniofacial development. These studies will help us to understand the role of vgl-2a in the development of the zebrafish cranial skeleton and contribute to our knowledge of vertebrate craionfacial development and perhaps the etiology of human Craniofacial disorders.
|Johnson, Christopher W; Hernandez-Lagunas, Laura; Feng, Weiguo et al. (2011) Vgll2a is required for neural crest cell survival during zebrafish craniofacial development. Dev Biol 357:269-81|