Gap junctional communication during zebrafish fin growth

斑马鱼鳍生长过程中的间隙连接通讯

• 批准号: 7048627
• 负责人: Mary Kathryn Iovine
• 金额: $ 22.15万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048627
• 关键词: HeLa cells; alleles; bone development; cardiogenesis; cell cell interaction; cell differentiation; cell proliferation; developmental genetics; gap junctions; gene expression; genetic regulation; immunofluorescence technique; membrane channels; osteoblasts; phenotype; protein localization; protein structure function; zebrafish

DESCRIPTION (provided by applicant): Zebrafish fins provide an excellent model system for revealing the molecular mechanisms controlling size and shape. Fins grow by the addition of bony segments to the distal ends of growing fin rays. Therefore, fin length mutants that produce short segments may identify molecules that regulate bone morphogenesis. Indeed, the short fin mutant produces short fin ray segments, and this phenotype is caused by mutations in zebrafish connexin43. Interestingly, mutations in human connexin43 cause oculodentodigital dysplasia, a syndrome which results in craniofacial and limb malformations. Thus, connexin43 controls the morphology of dermal bone in both zebrafish and humans, and may therefore play similar roles in the regulation of size and shape in these tissues. The underlying goal of this proposal is to correlate the function of connexin43 with the cellular and molecular events of segment morphogenesis. This will be accomplished by four aims. First, several new alleles of connexin43 that modify or limit gap junction intercellular communication will be generated. Second, gap junction communication will be monitored in different alleles of connexin43 in a heterologous assay for cell-cell communication. Third, connexin43 expression will be monitored with respect to the cellular events required for segment morphogenesis, such as cell proliferation and osteoblast differentiation. Finally, the cellular basis for short segments will be examined by monitoring these processes in short fin mutants. Thus, the aims of this proposal will provide immediate insights into the control of bony segment growth in zebrafish. Furthermore, these insights will directly facilitate future understanding of the biology of human bone malformations.

描述（由申请人提供）：斑马鱼鳍提供了一个优秀的模型系统，用于揭示控制尺寸和形状的分子机制。鳍是通过在生长的鳍条远端添加骨段而生长的。因此，产生短片段的鳍长度突变体可能会识别调节骨形态发生的分子。事实上，短鳍突变体产生短鳍射线片段，这种表型是由斑马鱼连接蛋白43的突变引起的。有趣的是，人类连接蛋白 43 的突变会导致眼齿指发育不良，这是一种导致颅面和肢体畸形的综合征。因此，connexin43 控制斑马鱼和人类真皮骨的形态，因此可能在调节这些组织的大小和形状方面发挥相似的作用。该提案的根本目标是将 connexin43 的功能与节段形态发生的细胞和分子事件相关联。这将通过四个目标来实现。首先，将产生几个新的 connexin43 等位基因，它们会修改或限制间隙连接细胞间通讯。其次，将在细胞间通讯的异源测定中监测 connexin43 的不同等位基因中的间隙连接通讯。第三，将监测节段形态发生所需的细胞事件（例如细胞增殖和成骨细胞分化）方面的连接蛋白43表达。最后，将通过监测短鳍突变体中的这些过程来检查短片段的细胞基础。因此，该提案的目的将为斑马鱼骨节生长的控制提供直接的见解。此外，这些见解将直接促进未来对人类骨骼畸形生物学的理解。