Genetic Basis of Patterning and Growth in Drosophila Eye

在多细胞生物中，器官单层上皮的转变需要轴向模式 通过描绘前后（AP），背腹（DV）和 近端-远端（PD）轴。我们采用果蝇眼模型来研究高度的 （轴向）DV图案化和生长的保守的基本过程。在眼睛发育过程中， 先于AP和PD轴图案化，并形成背侧和腹侧隔室。之间的边界 眼的背侧和腹侧区域，称为赤道，是Notch（N）信号传导上调的位点， 其调节细胞增殖和分化。辨别轴线确定（DV）的机制是 对于我们理解器官发生至关重要，因为DV描绘的问题导致发育/ 从苍蝇到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， 是由背侧选择基因和腹侧基因的相互作用建立的。果蝇的眼睛开始于 从腹侧等同状态开始，背侧命运通过GATA家族的表达开始建立， 转录因子Pannier（Pnr）、分泌型形态发生蛋白Wingless（Wg）和易洛魁族（Iro-C）家族蛋白。 在背侧眼中，pnr不是Wg表达的唯一调节因子。它强烈表明可能还有其他的 背眼基因还有待鉴定。为了了解DV模式的分子遗传基础， 我们将分析（1）确定新的背眼基因dve在眼睛发育中的作用，（2） 探讨背眼图案化基因的遗传层次;（3）DV图案化与Hippo 信号传导可在DV图案化期间共调节Wg。鉴于遗传机制是保守的，我们 他们还将测试SATB 1的作用，SATB 1是眼睛中dve的人类直系同源物，已知与生长有关 调节、癌症和转移。这些研究将有助于辨别（a）dve在轴向模式中的新作用， 视网膜分化的复杂过程，（B）dve在描绘眼睛与头部边界中的作用，以及（c） 参与生长和癌症的基因确实在模式和分化中起作用，（d）如何独立地 通路相互作用，以调节发育中的眼睛的生长和模式。这些研究将具有重大意义。 （i）人类基因突变引起的发育缺陷的分子基础 果蝇dve同源物，以及（ii）果蝇器官发生早期发育事件的遗传机制 更高级的脊椎动物。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 投射到大脑。这些研究将阐明早期发育事件在视网膜病变中的作用。 在正常发育和疾病期间轴突投射到大脑。从这些产生的知识 这些研究有望阐明正常视觉功能形成和发育的基本机制 并且在视网膜疾病和眼睛中的出生缺陷的背景下。

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.