Role of Endothelins in Skeletal Patterning in Zebrafish

内皮素在斑马鱼骨骼图案形成中的作用

• 批准号: 6634692
• 负责人: Thomas F Schilling
• 金额: $ 22.22万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634692
• 关键词: biological signal transduction; bone development; cartilage development; cell cell interaction; craniofacial; developmental genetics; embryo /fetus cell /tissue; endoderm; endothelin; gene expression; gene mutation; genetic mapping; histogenesis; hormone receptor; hormone regulation /control mechanism; mesoderm; molecular cloning; mutant; neural crest; oral pharyngeal; osteogenesis; protein tyrosine kinase; receptor expression; tissue mosaicism; zebrafish

DESCRIPTION (Adapted from the Investigator's Abstract): Craniofacial defects result from disruptions of the normal mechanisms that control head development. Thus understanding the basis for inherited craniofacial disorders requires knowledge of the embryonic molecular and genetic processes that direct pattern formation in the head. These include the tissue interactions that establish skeletogenic mesenchyme, its condensation and differentiation into cartilages and bones, and their interconnections to form a functional skeletal network. This proposal examines these issues using the genetics and embryological advantages of zebrafish as a model. Zebrafish embryos form a simple, segmentally organized pharyngeal skeleton, where homologies with human skeletal elements are recognizable, and many of the genes that pattern these segments have been conserved between fish and humans. It is thought that a major component of patterning within each pharyngeal segment is endothelin-1 (Et-1), a signal that directs patterns of chondrogenesis and osteogenesis. Experiments are proposed to dissect the role of this signal using a set of zebrafish mutants including one mutant in Et-1 itself as well as mutants and antagonists of Et receptors. Aim 1 is to characterize genes of the ephrin and eph receptor tyrosine kinase families that we have implicated in controlling neural crest morphogenesis and their responses to Et-1. Aim 2 is to analyze one mutant called schmerle, which phenotypically resembles loss of Et-1 function, in more detail and to clone its underlying genetic basis. Aim 3 focuses on defining which specific tissue interactions require Et-1, between either the pharyngeal epithelium or mesoderm and the skeletogenic neural crest, by using cell transplantation in Et-1 mutants to dissect the biochemical basis for skeletal patterning.

描述（改编自研究者摘要）：颅面缺损