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: 7390613
• 负责人: Mary Kathryn Iovine
• 金额: $ 21.18万
• 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/7390613
• 关键词: Alleles; Biological Assay; Biological Models; Cell Communication; Cell Count; Cell Proliferation; Cell division; Cells; Communication; Connexin 43; Defect; Dermal; Distal; Event; Exhibits; Fluorescent Dyes; Future; Gap Junctions; Genes; Goals; Growth; Hela Cells; Human; Human Biology; Length; Limb structure; Missense Mutation; Molecular; Monitor; Morphogenesis; Morphology; Mutation; Osteoblasts; Pathway interactions; Phenotype; Play; Process; Regulation; Role; Shapes; Syndrome; Testing; Tissues; Zebrafish; base; bone; craniofacial; insight; intercellular communication; intramembranous bone; intramembranous bone formation; malformation; mutant; oculodentodigital dysplasia; protein degradation; size; trafficking

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出色的模型系统，用于揭示控制大小和形状的分子机制。鳍是通过在生长的鳍光线的远端增加骨段来生长的。因此，产生短段的鳍长突变体可以鉴定调节骨形态发生的分子。实际上，短鳍突变体产生短鳍射线片段，该表型是由斑马鱼connexin43突变引起的。有趣的是，人类连接43的突变引起眼牙性牙本质发育不良，这是一种综合征，导致颅面和肢体畸形。因此，connexin43控制斑马鱼和人类皮肤骨的形态，因此在这些组织中的大小和形状的调节中可能起着相似的作用。该建议的基本目标是将连接蛋白43的功能与片段形态发生的细胞和分子事件相关联。这将由四个目标完成。首先，将生成几个修改或限制间隙连接界面通信的新等位基因。其次，将在异源分析中以用于细胞电池通信的异源测定中的不同等位基因中的差距连接通信。第三，将根据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）监测connexin43的表达。最后，将通过在短鳍突变体中监测这些过程来检查短段的细胞基础。因此，该提案的目的将为控制斑马鱼的骨段增长的控制提供直接的见解。此外，这些见解将直接促进对人骨畸形生物学的未来理解。