Genetic Basis of Patterning and Growth in Drosophila Eye

在多细胞生物体中，器官的单层上皮的过渡需要轴向图案化。 通过前-后(AP)、背-腹侧(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的 保守的(轴向)DV图案化和生长的基本过程。在眼睛发育期间，DV图案 在AP和PD轴模式之前，形成背侧和腹侧间隔。之间的边界 眼睛的背侧和腹侧区域，称为赤道，是Notch(N)信号上调的部位， 它调节细胞的增殖和分化。识别轴确定(DV)的机制是 对我们理解器官发生至关重要，因为DV描述的问题导致发育/ 苍蝇对人类的先天缺陷。我们的长期目标是了解DV模式的遗传基础 是由背部选择基因和腹面基因相互作用建立的。果蝇的眼睛开始了 从由GATA家族表达开始建立的背侧命运的腹侧等价状态 转录因子Pannier(Pnr)、分泌型形态发生蛋白Wg(Wg)和易洛魁(Iroquis，Iro-C)家族蛋白。 在背眼，PNR不是Wg表达的唯一调节因子。它强烈地表明，可能还有其他 尚未确定的背部眼基因。为了了解DV模式的分子遗传学基础， 我们将分析(1)确定新的背眼基因dve在眼睛发育过程中的作用，(2) 研究背部眼纹基因的遗传层级，以及(3)DV纹样和河马 在DV模式形成过程中，信号可能共同调节Wg。鉴于遗传机制是保守的，我们 还将测试SATB1的作用，这是一种人类眼睛中DVE的同源基因，已知与生长有关 调控、癌症和转移。这些研究将有助于识别(A)DVE在轴向图案化和 视网膜分化的复杂过程，(B)DVE在划定眼与头边界中的作用和(C) 参与生长和癌症的基因确实在模式形成和分化中起作用，(D)独立 这些通路相互作用，调节发育中的眼睛的生长和图案。这些研究将具有重要的意义 对理解(I)人类突变导致发育缺陷的分子基础的影响 果蝇Dve的同源基因，以及(Ii)果蝇器官发生过程中早期发育事件的遗传机制 高等脊椎动物也是。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 对大脑的投射。这些研究将阐明早期发育事件在视网膜中的作用 在正常发育和疾病期间，轴突投射到大脑。从这些方面产生的知识 研究有望阐明正常视觉功能形成和发育的基本机制 在视网膜疾病和眼睛出生缺陷的背景下。

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.