Genetic Basis of Patterning and Growth in Drosophila Eye

果蝇眼睛图案和生长的遗传基础

基本信息

批准号：
9377402
负责人：
AMIT SINGH
金额：
$ 43.95万
依托单位：
UNIVERSITY OF DAYTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9377402
关键词：
Active Learning Binding Binding Sites Biological Process Brain Cell Differentiation process Cell Lineage Cell Proliferation Cells Chromatin Code Collection Complex Congenital Abnormality Defect Development Differentiation and Growth Dimensions Disease Distal Dorsal Drosophila eye Drosophila genus Drosophila melanogaster Ectopic Expression Enhancers Epithelium Etiology Event Eye Eye Development Family Generations Genes Genetic Genetic Epistasis Genetic Transcription Genetic study Goals Growth Head Health Homeodomain Proteins Homologous Gene Human Knowledge Lead Light Malignant Neoplasms Modeling Molecular Molecular Genetics Mono-S Mutation Neoplasm Metastasis Organ Organism Organogenesis Orthologous Gene Pathway interactions Pattern Phenotype Phosphotransferases Play Primordium Process Protein Family Proventriculus Regulation Regulator Genes Regulatory Pathway Research Retina Retinal Retinal Defect Retinal Diseases Role Signal Pathway Signal Transduction Site Testing Transcription Coactivator Transgenic Organisms Up-Regulation Vertebrates Vision Visual system structure design early childhood experimental study fly gene conservation insight loss of function monolayer morphogens notch protein paracrine retinal axon spatiotemporal three dimensional structure transcription factor undergraduate student

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 employ 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. The border between the dorsal and the ventral domains of eye, termed equator, is the site for upregulation of the Notch (N) signaling, which regulates cell proliferation and differentiation. 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. To understand the molecular genetic basis of DV patterning, we will analyze the (1) Determine the role of new dorsal eye gene dve during eye development, (2) Investigate genetic hierarchy of dorsal eye patterning genes, and (3) Whether DV patterning and Hippo signaling may co-regulate Wg during DV patterning.. Given that the genetic machinery is conserved, we will also test the role of SATB1, a human ortholog of dve in the eye, which is known to be involved in growth regulation, cancer and metastasis. These studies will help discern (a) a new role of dve in axial patterning and complex process of retinal differentiation, (b) role of dve in delineating eye versus head boundary and (c) genes involved in growth and cancer do have function in patterning and differentiation, (d) How do independent pathways interact to regulate growth and patterning in the developing eye?. These studies will have significant bearings on understanding the (i) molecular basis of developmental defects caused by mutations in the human homolog of Drosophila dve, and (ii) genetic mechanism of early developmental events during organogenesis in higher vertebrates too. In humans and other vertebrates, DV polarity of the retina regulate the retinal axon projections to the brain. These studies will shed light on the role of early developmental events on the retinal axon projection to the brain during normal development and disease. 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，轴向图案是需要轴向模式的通过描绘前后验（AP），多索 - 腹部（DV）和 proximo-Distal（PD）轴。我们采用果蝇Melanogaster（果蝇）眼睛模型来研究高度（轴向）DV模式和生长的保守基本过程。在眼睛开发期间，DV图案先于AP和PD轴图案，并形成背侧和腹侧室。边界眼睛和腹侧域（称为赤道）是上调Notch（n）信号的位点，调节细胞增殖和分化。辨别轴确定的机理（DV）为对于我们对器官发生的理解至关重要，因为DV描述的问题会导致发育/ 苍蝇的出生缺陷。我们的长期目标是了解DV图案的遗传基础通过背侧选择器基因和腹侧基因的相互作用建立。果蝇的眼睛开始从腹侧等效状态，通过GATA家族表达的发作建立背命运转录因子PANNIER（PNR），分泌的形态学无翼（WG）和iroquois（IRO-C）家族蛋白。在背眼中，PNR不是WG表达的唯一调节剂。强烈表明可能还有其他背眼基因尚待鉴定。要了解DV模式的分子遗传基础，我们将分析（1）确定眼睛发育过程中新的背眼基因的作用，（2）研究背眼图案基因的遗传层次结构，以及（3）DV图案和河马是否存在信号传导可能在DV模式期间共同调节WG。鉴于遗传机制是保守的，我们还将测试satb1的作用，satb1是眼睛中的人类直系同源物，已知与生长有关调节，癌症和转移。这些研究将有助于（a）DVE在轴向图案中的新作用，视网膜分化的复杂过程，（b）DVE在描绘眼与头部边界的作用，（c）与生长和癌症有关的基因确实在模式和分化中具有起作用，（d）独立途径相互作用以调节发育中的眼睛中的生长和模式。这些研究将具有重要的了解人类突变引起的（i）分子基础的（i）分子基础果蝇DVE的同源物，以及（ii）在器官发生过程中早期发育事件的遗传机制脊椎动物也更高。在人类和其他脊椎动物中，视网膜的DV极性调节视网膜轴突对大脑的预测。这些研究将阐明早期发展事件在视网膜上的作用正常发育和疾病期间，轴突投射到大脑。从这些产生的知识预计研究将阐明正常视觉功能的模式和增长中的基本机制在视网膜疾病和眼睛的先天缺陷的背景下。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An E3 ubiquitin ligase, cullin-4 regulates retinal differentiation in Drosophila eye.

DOI：
10.1002/dvg.23395
发表时间：
2020-11
期刊：
GENESIS
影响因子：
1.5
作者：
Tare, Meghana;Chimata, Anuradha Venkatakrishnan;Gogia, Neha;Narwal, Sonia;Deshpande, Prajakta;Singh, Amit
通讯作者：
Singh, Amit

Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila.