The role of Protocadherin-17 in the development of direction selective circuits in the zebrafish visual system

摘要 在发育过程中，神经祖细胞分裂产生新生神经元，这些神经元迁移和延伸 轴突和树突。这些神经元与它们的邻居形成突触，并开始组装功能 神经回路，随着突触连接的完善和额外的神经元被整合到这些回路中， 电路.这些装配过程中的缺陷会导致广泛的问题，包括视觉问题。 加工障碍原钙粘蛋白-17（Pcdh 17）是一种嗜同性细胞粘附分子， 杏仁核轴突的集体生长和介导体外接触依赖性轴突生长，以及 短期突触可塑性我们的初步数据显示，在幼虫的视顶盖电路水平的缺陷 斑马鱼，方向选择性神经元的比例减少，非选择性神经元的比例增加。 神经元我们还提供了数据表明，视顶盖的神经元可以束状和共同树枝状 在电路形成期间。我们假设Pcdh 17粘附的丧失导致了乔木模式的改变， 生长和突触发生，这降低了神经元反应的选择性。在这 发展/探索R21，我们将研究：1）视觉反应的发展轨迹， pcdh 17突变体，以更好地确定这些反应何时以及如何从野生型幼虫分化，和2） 野生型和突变体中轴突和树突乔木生长和突触发生的发育轨迹 幼虫这些结果可能揭示了一种新的局部电路组装的细胞机制， 深入了解细胞生长过程如何控制神经反应的成熟。

ABSTRACT During development, neural progenitors divide to produce nascent neurons, which migrate and extend axons and dendrites. These neurons form synapses with their neighbors and begin to assemble functional circuits, which mature as synaptic connectivity is refined and additional neurons are integrated into these circuits. Defects in these assembly processes can result in a broad range of problems, including visual processing disorders. Protocadherin-17 (Pcdh17) is a homophilic cell adhesion molecule that is important for collective outgrowth of amygdala axons and to mediate contact-dependent axon growth in vitro, as well as short-term synaptic plasticity. Our preliminary data show circuit-level defects in the optic tectum of the larval zebrafish, with a decrease in the proportion of direction selective neurons and an increase of non-selective neurons. We also provide data showing that neurons of the optic tectum can fasciculate and co-arborize during circuit formation. We hypothesize that loss of Pcdh17 adhesion results in altered patterns of arbor growth and synaptogenesis, which degrades the selectivity of neuronal responses. In this developmental/exploratory R21, we will examine: 1) the developmental trajectory of visual responses in pcdh17 mutants to better define when and how these responses diverge from wild type larva, and 2) the developmental trajectories of axonal and dendritic arbor growth and synaptogenesis in wild type and mutant larvae. These results could reveal a novel cellular mechanism for the assembly of local circuitry and provide insight into how cellular growth processes govern the maturation of neural responses.