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Mechanisms of C. elegans Gastrulation

线虫原肠胚形成的机制

基本信息

批准号：
7628940
负责人：
ROBERT P GOLDSTEIN
金额：
$ 27.65万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7628940
关键词：
Actomyosin Adhesions Animals Apical Behavior Biological Assay Cadherins Caenorhabditis elegans Candidate Disease Gene Cells Complex Cytoskeleton Defect Development Developmental Delay Disorders Disease Dissection Drosophila genus Enhancers Eye diseases Funding Future Genes Genetic Goals Grant Homologous Gene Human Lateral Lead Life Link Malignant Neoplasms Modeling Molecular Morphogenesis Neural Tube Closure Neural Tube Defects Neural tube Organ Organism Pattern Phenotype Play Positioning Attribute Process Proteins RNA Interference Research Role Shapes Side Signal Transduction Signaling Molecule Skin Study models System Tertiary Protein Structure Testing Tissues Work Xenopus Zebrafish base cell motility chromosome 3p deletion syndrome congenital heart disorder contactin expectation gastrulation gene function human disease imaging modality improved insight interest loss of function microphthalmia-dermal aplasia-sclerocornea syndrome novel precursor cell protein function rho rho GTPase-activating protein

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：