Morphogenetic processes such as gastrulation, neurulation, and the shaping of organs play critical roles in animal development. We have worked to develop C. elegans gastrulation as a new model for studying mechanisms of morphogenesis. The goal of our research is to use this model to understand some of the mechanisms that can position cells during morphogenesis. We pursue these mechanisms by combining cell manipulations, as has been successful in systems like Xenopus and chick, with genetics, as has been successful in C. elegans, Drosophila and zebrafish. Our expectation is that the ability to combine genetics and cell manipulations in a single system, together with modern live imaging methods, to study a simple model of morphogenesis, will enable us to make some unique and important contributions to understanding mechanisms of morphogenesis. C. elegans gastrulation begins with the internalization of two endodermal precursor cells. Our preliminary studies have implicated contraction of an apical actomyosin meshwork in these cells in their internalization. Our studies have also provided a set of assays that can facilitate thorough dissection of function for new genes. We will (1) determine how a set of adhesion proteins regulates cell movements in gastrulation, (2) determine how adhesion proteins and intracellular signaling molecules contribute together to gastrulation, and (3) based on our results identifying new genes to date, screen for and pursue additional genes that function in the processes studied above. We expect that this model can inform how the cellular and molecular mechanisms of morphogenesis may be disrupted in certain human diseases, most notably in neural tube defects, as neural tube formation and C. elegans gastrulation share certain cellular and molecular mechanisms. Project narrative: We have worked to develop C. elegans gastrulation as a new model for studying mechanisms of morphogenesis, combining genetics, modern live imaging methods, and direct manipulations of cells. The overall goal of our research is to understand the mechanisms that position cells in C. elegans gastrulation, to further understand mechanisms of morphogenesis common to all animals including humans. We expect that this simple model can inform our understanding of cellular and molecular mechanisms of morphogenesis in disease states such as neural tube defects, cancer, and congenital heart disease. More specifically, one of the genes we are studying, rig-6, is the C. elegans homolog of a human gene that has been implicated in developmental delay associated with 3p deletion syndrome. Another gene we are studying, a RhoGAP called C01F4.2, is the C. elegans homolog of ARHGAP6, a protein implicated in a human skin and eye disease called microphthalmia with linear skin defects. Study of these genes'functions in C. elegans may provide valuable insights into possible functions of the human homologs.
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