Genetic Basis of Dorso-Ventral Patterning in the Drosophila Eye

果蝇眼背腹模式的遗传基础

• 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
• 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

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，轴向图案是需要轴向模式的 通过描绘前后（AP），dorso-dentral的划分到三维器官的器官原始 （DV）和proximo-Distal（PD）轴。我们使用果蝇Melanogaster（果蝇）眼模型来研究 （轴向）DV模式和生长的高度保守基本过程。在眼睛发育期间，DV 构图先于AP和PD轴图案，并形成背侧和腹侧室。辨别 轴确定机制（DV）对于我们对器官发生的理解至关重要 DV描述的问题导致人类苍蝇的发育/先天缺陷。我们的长期 目标是了解通过背侧相互作用建立的DV图案的遗传基础 选择器基因和腹基因。果蝇的眼睛从腹侧等效状态开始 通过GATA家庭转录因子Pannier的表达发作来确定背侧命运 （PNR），分泌的形态学无翼（WG）和iroquois（IRO-C）家族蛋白。在背面，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 尚待确定。我们已经确定了一个新的背眼选择器缺陷Proventriculus（DVE）， 转录因子，其作用于WG的上游。了解DV的分子遗传基础 图案化，我们将分析（1）研究背部眼中的WG调节。 （2）如何WG 视眼与头部命运解释了背面的梯度吗？ （3）测试河马信号是否共同 用眼睛中的DV模式基因调节WG信号传导。鉴于遗传机械是 保守的，我们还将测试SATB1的作用，Satb1是DVE的人类直系同源物。我们的研究将有 沿dv的（i）谱系限制和图案的发展机制有很大的关系 在器官发生过程中的图案，（ii）生长调节基因在模式和（iii）中的作用 对幼儿视网膜疾病的病因的理解。 （iv）独立途径如何相互作用 在发育中的眼睛中调节生长和图案？拟议的研究将对 （1）背部眼基因如何通过调节WG信号传导来确定眼睛与头部命运，（2） 两种独立的途径，例如河马信号传导和DV模式核心审查WG信号，以促进 发育中的生长和图案？ （3）SATB1主要众所周知，可以调节生长和我们 眼中的研究将洞悉SATB1的生长调节和模式化功能。这些研究 了解早期发育事件的遗传机制将具有重要意义 在较高脊椎动物的器官发生过程中。这些研究产生的知识有望 阐明正常视觉功能模式和增长的基本机制以及 视网膜疾病和眼睛出生缺陷的背景。