Neurogenesis of the optic lobes

 描述(申请人提供)：果蝇视叶中的四个神经结构(板层、髓质、小叶和小叶复合体)通过以视网膜定位方式组织的特殊细胞类型的神经网络顺序地处理视觉信息。我们将继续我们的研究，以了解发育中的视叶是如何产生神经元多样性的，视叶由100多种细胞类型组成。我们的观察表明，延髓中的神经元规范是三种机制整合的结果：(I)800神经母细胞表达一系列时间转录因子，随着年龄的增长产生不同类型的神经元，每个神经元接触由光感受器支配的800列中的一列。(Ii)时间序列被区域转录因子局部修改，并产生支配多个列的神经元。(Iii)通过Notch进行的二元命运选择进一步使 终末细胞分裂。在发育中的延髓的最后端区域和小叶复合体的前体区域，神经发生因不同的 转录因子不仅能决定神经元的命运，还能控制神经元分裂的前驱模式和神经元的死亡或存活。这说明了复杂的大脑结构如何使用不同的策略来适应和产生正确数量的具有适当特征的特定细胞类型。我们将研究控制这种神经发生的机制。目的1：神经母细胞的时间演变：时间和过渡机制时间模式是在果蝇和脊椎动物中产生神经多样性的一般机制。我们将探索控制延髓中神经母细胞时间进程的分子过程。目的2.延髓神经上皮细胞的区域化和神经母细胞的特化我们将研究在延髓前体域的不同区域改变时间序列输出的规则。这使得局部产生的迁移神经元占据了整个髓质。目的3.转录因子表达与神经元特征的相关性为了了解转录网络如何控制神经元的特征，我们将使用大规模的单细胞转录切割来识别调控相互作用，并确定这些相互作用如何定义每个神经元的身份。目的4.时间模式对神经母细胞分裂模式和神经元存活或死亡的调节我们将研究时间转录因子如何作用于细胞周期和促凋亡基因，以表征视叶不同部分产生特殊神经元的不同策略。目的5.小叶复合体前体细胞的非时间模式非依赖性神经发生我们将通过控制神经母细胞的快速退出增殖来探索控制不同的神经发生模式的分子机制，该模式产生3种类型的无时间序列的小叶神经元。这项雄心勃勃的工作将使我们能够确定神经模式和多样性产生的基本原则，这对苍蝇和脊椎动物的其他神经系统具有广泛的影响。

 DESCRIPTION (provided by applicant): Four neural structures in the Drosophila optic lobes (lamina, medulla, lobula and lobula complex) sequentially process visual information through neural networks of specialized cell types organized in a retinotopic manner. We will continue our investigations to understand how neuronal diversity is generated in the developing optic lobes, which are comprised of more than 100 cell types. Our observations suggest that neuronal specification in the medulla results from the integration of three mechanisms: (i) 800 neuroblasts express a sequence of temporal transcription factors to generate distinct types of neurons as they age, each contacting one of the 800 columns innervated by photoreceptors. (ii) The temporal series is modified locally by regional transcription factors and produces neurons that innervate multiple columns. (iii) Binary fate choice via Notch further diversifies daughters of the terminal cell division. In the posterior-most region of the developing medulla and in the progenitor region of the lobula complex, neurogenesis differs significantly with a different set of transcription factors that act not only to specify neuronal fate but also to control the precursor mode of division and the death or survival of neurons. This illustrates how complex brain structures use different strategies to adapt and produce the correct number of specific cell types with the appropriate characteristics. We will investigate the mechanisms controlling this neurogenesis. Aim 1: Temporal progression of neuroblasts: Timing and transition mechanisms Temporal patterning is a general mechanism to generate neural diversity in flies and vertebrates. We will explore the molecular processes controlling the temporal progression of neuroblasts in the medulla. Aim 2. Regionalization of the medulla neuroepithelium and specialization of neuroblasts We will investigate the rules that modify the output of the temporal series in different regions of the medulla progenitor domain. This allows the local production of neurons that migrate to occupy the entire medulla. Aim 3. Correlation between transcription factor expression and neuronal characteristics To understand how transcription networks control the characteristics of neurons, we will use large-scale single cell transcriptomics to identify regulatory interactions and determine how these define the identity of each neuron. Aim 4. Regulation of the mode of neuroblast division and neuronal survival or death by temporal patterning We will investigate how temporal transcription factors act on the cell cycle and on pro-apoptotic genes to characterize the different strategies used by distinct parts of the optic lobes to produce specialized neurons. Aim 5. Temporal patterning-independent neurogenesis in lobula complex progenitors We will explore the molecular mechanisms that control a different mode of neurogenesis that produces 3 types of lobula neurons without a temporal series by controlling the rapid exit of neuroblasts from proliferation. This ambitious work will allow us to identify basic principles of neural patterning and diversity generation, which have broad implications for other neuronal systems in flies and vertebrates.