Genetic Basis of Dorso-Ventral Patterning in the Drosophila Eye

在多细胞生物体中，轴向图案化是细胞的单层上皮转变所必需的。 通过描绘前后（AP）、背腹（dorso-ventral） (DV)和近端-远端（PD）轴。我们使用果蝇（Drosophila melanogaster）眼模型来研究 （轴向）DV图案化和生长的高度保守的基本过程。在眼睛发育过程中，DV 图案化先于AP和PD轴图案化，并形成背侧和腹侧隔室。挑剔 轴决定（DV）的机制对于我们理解器官发生是至关重要的， DV描绘的问题导致从果蝇到人类的发育/出生缺陷。我们的长期 目的是了解DV模式的遗传基础，DV模式是通过背侧肌和背侧肌的相互作用建立的。 选择基因和腹侧基因。果蝇的眼睛从腹侧的等效状态开始， 其背侧命运通过GATA家族转录因子Pannier的表达开始建立， (Pnr)分泌型形态发生蛋白Wingless（Wg）和Iroquois（Iro-C）家族蛋白。在背侧的眼睛里， 不是Wg表达的唯一调节因子。这强烈表明可能还有其他的背眼基因 尚未被确认我们发现了一种新的背侧眼选择器缺陷前胃（dve）， 转录因子，其作用于WG的上游。了解DV的分子遗传学基础 图案化，我们将分析（1）研究背眼中的wg调节。(2)如何Wg 从背侧眼的梯度被解释为眼与头的命运？(3)测试河马信号是否合- 用眼睛中的DV图案化基因调节Wg信号传导。鉴于遗传机制是 保守，我们也将测试SATB 1的作用，SATB 1是眼睛中dve的人类直系同源物。我们的研究将有 与（i）DV后谱系限制和模式化的发育机制有重要关系 在器官发生过程中的模式化，（ii）生长调节基因在模式化中的作用，以及（iii） 了解儿童早期视网膜疾病的病因。(iv)独立的通路如何相互作用 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与头部的命运，（2）如何 两个独立的途径，如Hippo信号传导和DV模式共同调节Wg信号传导，以促进 在发育中的眼睛中生长和形成图案？(3)已知SATB 1主要调节生长， 对眼睛的研究将为深入了解SATB 1的生长调节和图案功能提供帮助。这些研究 将对理解早期发育事件的遗传机制具有重要意义 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预计将 阐明正常视觉功能的模式和生长的基本机制， 视网膜疾病和先天缺陷的背景下在眼睛。

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.