Genetic Control of Symmetry in the Eye

眼睛对称性的遗传控制

• 批准号: 7486851
• 负责人: Richard Lee Kelley
• 金额: $ 35.68万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486851
• 关键词: 3-Phosphoinositide Dependent Protein Kinase-1; Adaptor Signaling Protein; Address; Apoptosis; Binding; Biochemical Genetics; C-terminal; Cell Death; Cell Survival; Cells; Complex; Data; Differentiation and Growth; Dorsal; Down-Regulation; Drosophila genus; Essential Genes; Etiology; Event; Eye; Eye Development; Family; Gene-Modified; Genes; Genetic; Genetic Models; Goals; Golgi Apparatus; Growth; Growth and Development function; Homeodomain Proteins; Human Genetics; Ligands; Lobe; Localized; Mammals; Mediating; Modeling; Molecular; Molecular Genetics; Mothers; Notch Signaling Pathway; Organ; Pathway interactions; Pattern; Phenotype; Phosphorylation; Phosphotransferases; Play; Primordium; Proteins; Regulation; Research Personnel; Retinal; Retinal Diseases; Role; Signal Transduction; Specific qualifier value; System; Testing; Transcription Coactivator; Transferase; Ubiquitin-Conjugating Enzymes; base; cell growth; early childhood; eye primordia; gene function; genetic analysis; imaginal disc; in vivo; morphogens; mutant; notch protein; novel; prevent; transcription factor; ubiquitin ligase; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): Axial patterning in organ primordium is essential for its growth and development. The fruit fly, Drosophila, provides an ideal model for genetic analysis of dorsoventral (DV) patterning and growth of the eye primordium. Our goal is to utilize this powerful genetic system to identify key genes involved in early eye patterning and reveal the molecular mechanisms of genetic interactions underlying this important event which marks first lineage restriction in developing eye. In early eye imaginal disc, the DV patterning is established by initiation of expression of a dorsal selector gene, pannier (pnr), which controls the expression of wingless (wg) signaling gene and Iroquois family transcription factors. The dorsal genes antagonize the function of ventral genes including Lobe (L), Serrate (Ser) and fringe (fng). The interaction of these two groups of genes leads to preferential activation of Notch signaling at the DV border to induce growth and differentiation. One of the major questions to be addressed is the molecular genetic basis for such regulatory interactions. Based on antagonistic relationship between the dorsal and ventral genes, we propose that the major function of genes involved in DV patterning is to either promote or suppress the Pnr-mediated Wg signaling in the dorsal and ventral domains, respectively. These genes are further regulated by factors involved in the control of cell survival and/or cell growth. To test these hypotheses, we will analyze (i) relationship between L and Dpp in the negative regulation of Wg signaling, (ii) the function of L and Homothorax (Hth) in the control of eye growth and retinal fate determination, (iii) function of L and Cullin-4 ubiquitin ligase in the control of ventral cell survival, and (iv) the regulation of L function by Fng and Akt kinase in cell growth. Most of the genes studied here are highly conserved as they are present in higher mammals including humans, and genetic control of DV patterning is an important event during mammalian eye development. This study will help in revealing mechanisms of genetic interactions involved in early eye development. Thus, our study will also contribute to the understanding of mammalian eye development and etiology of early childhood retinal diseases.

描述（申请人提供）：器官原基的轴向结构对其生长发育至关重要。果蝇为眼原基的背腹侧（DV）模式和生长提供了一个理想的遗传分析模型。我们的目标是利用这个强大的遗传系统来识别参与早期眼睛模式的关键基因，并揭示这一重要事件背后的遗传相互作用的分子机制，这标志着眼睛发育中的第一谱系限制。