Dendritic patterning by interacting extrinsic cues

描述(申请人提供)：树突和轴突的范围决定了神经元在神经系统中接收和传递信息的方式，树突和轴突形态的破坏与许多神经疾病有关。许多类型的树突和轴突是根据瓦片和自我回避的原则组织的，在这种原则下，神经元的树枝扩张，直到它们毗邻邻近的树枝。自我回避和瓦片都确保神经系统中的感觉或突触输入被完全和非冗余地采样，这是功能神经元电路的关键要求，然而我们仍然对这些区域是如何构建的知之甚少。我们建议研究果蝇感觉系统中树突状瓦片的机制，这是一个研究神经元形态发生的分子控制的有力模型。我们建议研究控制树突平铺行为的树突-树突相互作用和树突-底物相互作用的分子基础。为了实现我们的目标，我们将进行激光细胞消融以消除神经元及其树突，以确定树突-树突相互作用是否对场形成重要。我们将使用基因敲除方法来消除基因的功能，并评估平铺的必要性，反过来，错误表达基因来确定它们是否足以促进平铺。我们将研究在轴突倾斜过程中对树突平铺至关重要的信号的重复使用，以探索树突和轴突是否由类似的细胞和分子机制形成图案。我们预计，这些结果将对理解神经系统中实现适当的树突和轴突模式的机制以及分子程序的改变或中断如何导致发育缺陷具有高度相关性。

DESCRIPTION (provided by applicant): The territories of dendritic and axonal arbors determine how neurons receive and transmit information in the nervous system, and disruptions of dendritic and axonal morphology are associated with numerous neurological disorders. Many types of dendrites and axons are organized according to the principles of tiling and self-avoidance, in which arbors of neurons expand until they abut neighboring arbors. Both self-avoidance and tiling ensure that sensory or synaptic inputs in the nervous system are sampled completely and non-redundantly, a critical requirement for functional neuronal circuits, however we still know little about how such territories are built. We propose to examine the mechanism of dendritic tiling in the Drosophila sensory system, a powerful model for studies of the molecular control of neuronal morphogenesis. We propose to examine the molecular basis for dendrite-dendrite interactions and dendrite-substrate interactions that control tiling behavior of dendrites To accomplish our aims we will perform laser cell ablations to eliminate neurons and their dendrites to determine whether dendrite-dendrite interactions are important for field formation. We will use gene knock out approaches to eliminate the function of genes and assess necessity for tiling, and, conversely, misexpress genes to determine whether they are sufficient to promote tiling. We will study the re-use of signals that are important for dendritic tiling during axon tilng to explore whether dendrites and axons are patterned by similar cellular and molecular mechanisms. We expect that these results will be highly relevant for understanding the mechanisms by which proper dendritic and axonal patterning is achieved in the nervous system, and how alteration or disruption of molecular programs might underlie developmental defects.