Pattern Formation in the Drosophila Eye Disc

Treisman 9728140 果蝇的眼睛由高度有序的相同亚单位阵列组成，每个亚单位包含一组确定的光感受器。光感受器的分化开始于幼虫眼的成虫盘的后缘，并逐渐向前发展，在这个过程中，需要由分化的光感受器分泌的刺猬（hh）蛋白的活性。分化的起始由TGF-β家族成员十肢麻痹（dpp）驱动，其在眼盘的后边缘和侧边缘表达。Wnt家族成员wingless（wg）的抑制作用，存在于侧缘，限制了后缘的启动。wg横向抑制dpp功能和dpp向后阻止wg表达的机制尚不清楚。Treisman博士建议通过研究dpp和wg信号通路的功能丧失或异位活性的影响来确定它们相互影响的分子基础。然后，她将研究dpp和wg是否受眼睛形成所需的五个基因的调节和介导。她还对影响眼睛大小和形状的新突变进行了筛查，这些突变可能会影响眼盘规格或图案所需的基因。这项筛选是通过在表型野生型杂合果蝇的眼睛中克隆纯合突变细胞来完成的，这使我们能够检查胚胎中也需要的基因在眼睛发育中的作用。Treisman博士计划描述这些突变的特征，并克隆眼盘细胞发育为视网膜组织所需的新基因。果蝇无眼、小鼠小眼和人类无虹膜编码的Pax-6蛋白之间观察到的结构和功能同源性证实了果蝇和脊椎动物眼睛发育的基本机制的相似性。这项研究有望鉴定出可能在脊椎动物和果蝇的发育中起作用的新分子。

Treisman 9728140 The Drosophila eye consists of a highly ordered array of identical sub-units, each containing a defined set of photoreceptors. Photoreceptor differentiation begins at the posterior margin of the larval eye imaginal disc and gradually progresses anteriorly, in a process which requires the activity of hedgehog (hh) protein secreted by the differentiated photoreceptors. The initiation of differentiation is driven by the TGF-Beta family member decapentaplegic (dpp), which is expressed at the posterior and lateral margins of the eye disc. The inhibitory effect of the Wnt family member wingless (wg), present at the lateral margins, restricts initiation to the posterior margin. The mechanisms by which wg inhibits the function of dpp laterally and dpp prevents the expression of wg posteriorly are not understood. Dr. Treisman proposes to determine the molecular basis for their effects on each other by studying the effects of loss of function or ectopic activity of components of the dpp and wg signaling pathways. She will then investigate whether dpp and wg are regulated by, and mediate the effects of, five genes that are required for eye formation. She has also conducted a screen for new mutations affecting the size and shape of the eye, which may affect genes required for eye disc specification or patterning. This screen was done by making clones of homozygous mutant cells in the eyes of phenotypically wild type heterozygous flies, allowing us to examine the role in eye development of genes that are also required in the embryo. Dr. Treisman plans to characterize these mutations and clone the novel genes that are required for cells in the eye disc to develop as retinal tissue. The observed structural and functional homology between the Pax-6 proteins encoded by Drosophila eyeless, mouse Small eye and human Aniridia confirms the similarity of the basic mechanisms underlying eye development in flies and vertebrates. This research is expected to identify novel molecules which are li kely to function in the development of vertebrates as well as of Drosophila.