Dendritic patterning by interacting extrinsic cues

描述（由申请人提供）：树突和轴突乔木的区域决定神经元如何在神经系统中接收和传递信息，树突和轴突形态的破坏与许多神经系统疾病相关。许多类型的树突和轴突是根据平铺和自我回避的原则组织的，其中神经元的乔木扩展直到它们邻接相邻的乔木。自我回避和平铺都确保了神经系统中的感觉或突触输入被完全和非冗余地采样，这是功能性神经元回路的关键要求，但我们仍然对这些领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平铺的机制，这是研究神经元形态发生的分子控制的有力模型。我们建议研究树突-树突相互作用和树突-基底相互作用的分子基础，这些相互作用控制树突的平铺行为。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很重要。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，相反，错误表达基因，以确定它们是否足以促进平铺。我们将研究在轴突tilng过程中对树突平铺很重要的信号的再利用，以探索树突和轴突是否由相似的细胞和分子机制形成图案。我们期望这些结果将与理解神经系统中实现适当的树突和轴突模式的机制高度相关，以及分子程序的改变或破坏可能是发育缺陷的基础。

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.