Genetic Basis of Dorso-Ventral Patterning in the Drosophila Eye

在多细胞生物中，单层上皮细胞的过渡需要轴向图案化。 器官原基到三维器官的前后部(AP)、背侧和腹侧的勾画 (DV)和近远端(Pd)轴。我们利用果蝇(果蝇)的眼睛模型来研究 高度保守的(轴向)DV图案化和生长的基本过程。在眼睛发育过程中，DV 图案化先于AP和PD轴图案化，形成背侧室和腹侧室。敏锐的眼光 轴决定(DV)的机制对于我们理解器官发生是至关重要的 DV描述的问题会导致苍蝇对人类的发育/出生缺陷。我们的长期计划 目的是了解DV模式的遗传基础，这种模式是由背部的相互作用建立的 选择器基因和腹侧基因。果蝇的眼睛从腹侧的等值状态开始 其背侧命运是由GATA家族转录因子Pannier的表达决定的 (PNR)、分泌型形态发生蛋白(Wg)和易洛魁(Iroquis，Iro-C)家族蛋白。在背部眼球，PNR 并不是Wg表达的唯一调节者。这有力地表明，可能还有其他背眼基因。 这些人的身份还没有确定。我们发现了一种新的背部眼球选择器缺陷腺胃(DVE)， 一种转录因子，作用于工作组的上游。了解DV的分子遗传学基础 模式，我们将分析(1)研究WG在背眼的调节。(2)工作方式 背部眼球的倾斜度解释为眼睛和头部的命运？(3)测试河马是否发出信号共同 通过眼睛中的DV模式基因调节Wg信号。鉴于遗传机制是 保守的话，我们还将测试SATB1的作用，这是一种人类DVE在眼睛中的同源基因。我们的研究将会有 显著影响(I)DV后的谱系限制和模式的发育机制 器官发生中的图案化，(Ii)生长调节基因在图案化中的作用和(Iii) 对儿童早期视网膜疾病病因的认识。(四)独立路径如何相互作用 来调节发育中的眼睛的生长和图案？拟议的研究将产生对以下方面的见解 (1)背眼基因如何通过调节Wg信号相互作用来决定眼睛和头部的命运，(2)如何 两条独立的途径，如河马信号和DV模式共同调节Wg信号促进 发育中眼睛的生长和图案？(3)SATB1主要调节生长和我们的 对眼睛的研究将为SATB1的生长调控和构图功能提供深入的见解。这些研究 将对理解早期发育事件的遗传机制有重大影响 在高等脊椎动物的器官发生过程中。从这些研究中产生的知识有望 阐明正常视觉功能形成和发育的基本机制以及 眼部的视网膜疾病和出生缺陷的背景。

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.