Discovering novel molecular genetic mechanisms that integrate morphogenesis and cell fate determination during vertebrate embryonic development

在脊椎动物胚胎发生过程中，一个不起眼的细胞球迅速增殖、生长，并积极地重新塑造成一个可识别的“成人”身体计划。这种显著的转变涉及细胞形状、模式和运动的无数变化，最终形成了像颅骨（颌骨和头骨）这样的复杂结构。这些事件的任何微小变化都可能极大地改变正常的形态。

During vertebrate embryogenesis, an unassuming ball of cells rapidly proliferates, grows, and is actively re-modeled into a recognizable 'adult' body plan. This remarkable transformation involves countless changes in cell shape, pattern and movement, which ultimately assemble complex structures like the cranioskeleton (jaws and skull). Slight changes to any of these events can dramatically alter normal form. My lab seeks to discover novel molecular and genetic mechanisms that control cranioskeletal patterning and morphogenesis. To this end, we undertook a collaborative and cross-disciplinary study to determine the genetic basis of extreme craniofacial diversity observed between purebred dog breeds (which are ideal for genetic studies of complex developmental traits). Our work identified many exciting new genes that are predicted to regulate craniofacial development - however, their actual activities remain unknown. In the following proposal, we use an elegant experimental model system - the zebrafish - to investigate candidate gene function. Zebrafish embryonic development is remarkably similar to that of mammals. However, zebrafish embryos are abundant, transparent, easily grown under a microscope, and we have established powerful techniques to actually image (in real time) the microscopic changes in cell structure and movement that occur during craniofacial development. Furthermore, zebrafish are well suited for genetic studies, and we can selectively and systematically "knockdown" gene function to study its effect on embryogenesis. Here, we employ cell biology, embryology, and classic genetic approaches in zebrafish to determine how our newly identified candidate genes control embryonic patterning and morphogenesis. Proposed research holds tremendous potential to expand our understanding of craniofacial development, and to identify novel molecular and cell biological mechanisms that co-ordinate extrinsic patterning cues with cell fate determination and cell movement during vertebrate embryonic development.