Mechanisms that underlie Drosophila visual center

在果蝇中，光感受器细胞将其轴突定位地发送到板层和延髓神经节。我们发现：1.DPP信号通过控制gcmm的表达，介导了正确的R轴突投射模式所需的板层胶质细胞的成熟。在DWNT4突变体中，视网膜腹侧轴突错误地投射到背板。正常情况下，DWNT4在发育中的视网膜板层的腹侧半部表达，DWNT4蛋白沿视网膜腹侧轴突表达。对Wnt信号成分的遗传分析表明，DWnt4对视网膜轴突的引导有直接作用。R轴突通过传递诱导信号Hedgehog(HH)触发板层神经元的增殖和分化。我们发现bHLH-PAS转录因子单一(Sim)是由HH在板层神经元中诱导的，是板层神经元与R轴突联系所必需的。在模拟突变体的大脑中，板层神经元无法与R轴突联系起来。这些数据揭示了一种调节轴突和神经元胞体之间相互作用的新机制，该机制建立了精确的神经元网络。R轴突通过称为视柄的管状结构支配视神经节，视柄由表面胶质细胞(SG)组成。视柄是独立于R轴突投射而自主形成的。我们发现编码粘着斑激酶(FAK)的Fak56D和CDGAPr在视杆的形成中起着重要的作用。延髓成神经细胞的发育具有一定的空间规律性，神经原基因之一的scute(L(1)sc)的致死作用标志着神经上皮细胞向成神经细胞的转变。L(1)sc的表达是一过性的，以同步有序的“原神经波”向更外侧的NE细胞方向发展。L(1)sc的表达足以诱导神经母细胞瘤的发生，是神经母细胞瘤发生分化所必需的。我们还发现，JAK/STAT信号在NE细胞中被激活，并负向调节前神经波的进展。

In Drosophila, photoreceptor cells topographically send their axons to the lamina and medulla ganglia.We found :1. DPP signaling mediates the maturation of the lamina glia required for the correct R axon projection pattern by controlling the expression of gcm.2. In DWnt4 mutants, ventral retinal axons misproject 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. Genetic analyses on Wnt signaling components suggest direct roles of DWnt4 for retinal axon guidance.3. 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. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks.4. R axons innervate optic ganglia through the tubular structure called the optic stalk, which consists of surface glia (SG). The optic stalk is formed autonomously, independently of R axon projection. We found Fak56D, encoding a Focal adhesion kinase (FAK) and CdGAPr play an important role in forming the optic stalk.5. Medulla neuroblasts develop sequentially in a spatially defined manner, and that lethal of scute (l(1)sc), one of the proneural genes, signals the transition of neuroepithelium to neuroblasts. L(1)sc expression is transient, progressing in a synchronized and ordered "proneural wave" that sweeps toward more lateral NE cells. L(1)sc expression is sufficient to induce NBs and is necessary for timely onset of NB differentiation. We also found that JAK/STAT signaling is activated in NE cells and negatively regulates proneural wave progression.