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Genetic Basis of Dorso-Ventral Patterning in the Drosophila Eye

果蝇眼背腹模式的遗传基础

基本信息

批准号：
10279832
负责人：
Madhuri Kango-Singh
金额：
$ 32.85万
依托单位：
UNIVERSITY OF DAYTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10279832
关键词：
3-Dimensional Affect Biological Assay Cell Lineage Cells Chromatin Congenital Abnormality Defect Development Differentiation and Growth Distal Dorsal Drosophila eye Drosophila genus Drosophila melanogaster Epithelial Etiology Event Eye Eye Development Family Generations Genes Genetic Genetic Epistasis Genetic Transcription Genetic study Goals Growth Head Health Homeodomain Proteins Human Knowledge Lead Modeling Molecular Genetics Neoplasm Metastasis Orbital separation excessive Organ Organism Organogenesis Orthologous Gene Pathway interactions Pattern Phenotype Play Primordium Process Protein Family Proventriculus Regulation Regulator Genes Retinal Defect Retinal Diseases Role Signal Pathway Signal Transduction Signaling Protein Testing Vertebrates Vision Visual Fields Visual system structure early childhood fly insight loss of function member monolayer morphogens paracrine spatiotemporal transcription factor

项目摘要

In multi-cellular organisms, axial patterning is required for transition of a mono-layered epithelium of an organ primordium to a three-dimensional organ by delineation of antero-posterior (AP), dorso-ventral (DV), and proximo-distal (PD) axis. We use Drosophila melanogaster (fruit fly) eye model to study the highly conserved fundamental process of (axial) DV patterning and growth. During eye development, DV patterning precedes AP and PD axis patterning, and forms dorsal and ventral compartments. Discerning the mechanism of axes determination (DV) is crucial for our understanding of organogenesis as the problems with DV delineation results in developmental/ birth defects in flies to humans. Our long term goal is to understand the genetic basis of DV patterning which is established by interactions of the dorsal selector genes and the ventral genes. The Drosophila eye begins from a ventral equivalent state on which the dorsal fate is established by onset of expression of GATA-family transcription factor Pannier (Pnr), the secreted morphogen Wingless (Wg), and Iroquois (Iro-C) family proteins. In the dorsal eye, pnr is not the sole regulator of Wg expression. It strongly suggests that there may be other dorsal eye genes that are yet to be identified. We have identified a new dorsal eye selector defective proventriculus (dve), a transcription factor, which acts upstream of wg. To understand the molecular genetic basis of DV patterning, we will analyze the (1) Investigate wg regulation in the dorsal eye. (2) How Wg gradient from dorsal eye is interpreted for eye versus head fate? (3) Test if Hippo signaling co- regulate Wg signaling with DV patterning genes in the eye. Given that the genetic machinery is conserved, we will also test the role of SATB1, a human ortholog of dve in the eye. Our study will have significant bearing on (i) developmental mechanisms of lineage restriction and patterning that follow DV patterning during organogenesis, (ii) role of growth regulatory gene in patterning and (iii) the understanding of etiology of early childhood retinal diseases. (iv) How do independent pathways interact to regulate growth and patterning in the developing eye? The proposed studies will generate insights into (1) how dorsal eye genes interact to determine eye versus head fate by regulating Wg signaling, (2) How two independent pathways like Hippo signaling and DV patterning coregulate Wg signaling to promote growth and patterning in the developing eye? (3) SATB1 is mainly known to regulate growth and our studies in eye will provide insight into growth regulation and patterning function of SATB1. These studies will have significant bearings on understanding the genetic mechanism of early developmental events during organogenesis in higher vertebrates. The knowledge generated from these studies is expected to elucidate fundamental mechanisms in patterning and growth of normal visual function and within the context of retinal disease and birth defects in the eye.

在多细胞生物中，细胞单层上皮的转变需要轴向模式