Studies on developmental mechanisms of the Drosophila visual center

果蝇视觉中枢发育机制的研究

基本信息

批准号：
15370093
负责人：
TABATA Tetsuya
金额：
$ 9.86万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15370093/
关键词：
Drosophila visual center R axon lamina neuron Dpp DWnt4 Hedgehog Sim 視覚系 b-HLH-PAS BMP 軸策投射 Notch Wnt

项目摘要

In Drosophila, photoreceptor cells topographically send their axons to the first optic ganglion, the lamina. 1.dpp is expressed at the margin of the lamina target region, where glial precursors reside. Inhibition of DPP signaling in this region resulted in defects in the differentiation of the lamina glial cells. Expression of glial cells missing (gcm) depends on DPP. In addition, R axon projections and lamina glia development were impaired by the expression of a dominant-negative form of gcm, suggesting that gcm controls the differentiation of lamina glial cells. These results suggest that DPP signaling mediates the maturation of the lamina glia required for the correct R axon projection pattern by controlling the expression of gcm. 2.R axons trigger proliferation and differentiation of lamina neurons by delivering the inductive signal, Hedgehog(Hh). We found that the bHLH-PAS transcription factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required for the association of lamina neurons with R axons. In sim mutant brains, lamina neurons fail to associate with R axons. As a result, lamina neurons are set aside from R axons. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks. 3. In DWnt4 mutants, ventral retinal axons misprojected to the dorsal lamina. DWnt4 is normally expressed in the ventral half of the developing lamina and DWnt4 protein was detected along ventral retinal axons. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes caused DWnt4-like defects, and were autonomously required in the retina, suggesting direct roles of DWnt4 for retinal axon guidance. In contrast, iroquois homeobox genes are the dorsal cues for the retina.

在果蝇中，感光细胞根据地形将轴突发送到第一个视神经节，即椎板。 1.dpp 在神经胶质前体所在的层板目标区域的边缘表达。抑制该区域的 DPP 信号传导会导致层状胶质细胞分化缺陷。神经胶质细胞缺失 (gcm) 的表达取决于 DPP。此外，R轴突投射和神经胶质层发育受到显性失活形式的gcm表达的损害，表明gcm控制神经胶质细胞层的分化。这些结果表明，DPP 信号传导通过控制 gcm 的表达来介导正确的 R 轴突投射模式所需的层状胶质细胞的成熟。 2.R轴突通过传递诱导信号Hedgehog(Hh)触发层神经元的增殖和分化。我们发现 bHLH-PAS 转录因子 Single-thought (Sim) 是由 Hh 在层层神经元中诱导的，并且是层层神经元与 R 轴突关联所必需的。在模拟突变大脑中，层神经元无法与 R 轴突关联。结果，层神经元与 R 轴突分开。这些数据揭示了一种调节轴突和神经元细胞体之间相互作用的新机制，从而建立精确的神经元网络。 3.在DWnt4突变体中，腹侧视网膜轴突错误投射到背侧层。 DWnt4 通常在发育中的椎板的腹侧一半中表达，并且沿腹侧视网膜轴突检测到 DWnt4 蛋白。 Dfrizzled2 和 dishevelled 分别编码 Wnt 信号传导所需的受体和信号分子。这两个基因的突变都会导致 DWnt4 样缺陷，并且是视网膜自主需要的，这表明 DWnt4 对视网膜轴突引导具有直接作用。相比之下，易洛魁同源框基因是视网膜的背侧线索。