Mauthner Cell Development in the Zebrafish Mutant

斑马鱼突变体的毛特纳细胞发育

• 批准号: 6316935
• 负责人: Michelle Gray
• 金额: $ 2.38万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6316935
• 关键词: Mauthner's neuron; behavioral genetics; confocal scanning microscopy; developmental genetics; developmental neurobiology; escape reaction; genetic mapping; motor neurons; mutant; neurogenetics; zebrafish

The precise regulation of neuronal cell number is essential for proper nervous system function. Mutants exhibiting excess neurons in discreet cell populations are useful for studying the genetic control of neuronal production. Moreover, mutants with extra neurons offer an opportunity to analyze the plasticity of neural circuit formation. We have isolated a mutation in zebrafish, loose ends (loe), that results in supernumerary Mauthner cells. Wild-type zebrafish have a bilateral pair of Mauthner cells on either side of the midline in hindbrain rhombomere 4. In contrast, loe mutants have on average five Mauthner cells on either side of the midline. By cloning the loe gene, we will reveal the identity of the molecule causing this defect. To this end, we will place loe on the genetic map of the zebrafish genome to determine whether it corresponds to a known gene. If a known gene is not revealed, we will positionally clone loe. We will also exploit the fact that loe has an increase in Mauthner cells to ask how the presence of these extra cells affects the formation of the escape response circuit. The escape response circuit involves sensory input onto Mauthner cells and Mauthner cell input onto primary motoneurons. We will characterize both the pre- and post-synaptic contacts in loe mutants to elucidate and how the circuit is organized differently due to the presence of extra Mauthner cells.

对神经细胞数量的精确调控对神经系统的正常功能至关重要。突变体在离散的细胞群体中表现出过多的神经元，这对于研究神经元产生的遗传控制是有用的。此外，具有额外神经元的突变体为分析神经回路形成的可塑性提供了机会。我们在斑马鱼中分离出了一种突变，即松散末端(LOE)，这种突变导致了多余的莫特纳细胞。野生型斑马鱼在后脑菱形核4的中线两侧都有一对莫特纳细胞。相比之下，LOE突变体在中线两边平均有五个莫特纳细胞。通过克隆LOE基因，我们将揭示导致这种缺陷的分子的身份。为此，我们将把LOE放在斑马鱼基因组的遗传图谱上，以确定它是否与已知基因相对应。如果一个已知基因没有被发现，我们将定位克隆LOE。我们还将利用LOE的Mauner细胞增加这一事实来研究这些额外细胞的存在如何影响逃逸反应电路的形成。逃逸反应回路包括对Mauthner细胞的感觉输入和对初级运动神经元的感觉输入。我们将表征LOE突变体中突触前和突触后的接触，以阐明由于额外的莫特纳细胞的存在，电路是如何不同地组织起来的。