formin Fmn2b 对于斑马鱼声惊反射回路中兴奋性中间神经元模块的发育是必需的。

The Formin Fmn2b Is Required for the Development of an Excitatory Interneuron Module in the Zebrafish Acoustic Startle Circuit.

机构信息

Indian Institute of Science Education and Research (IISER) Pune, Pune 411008, India.

Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

eNeuro. 2021 Jul 9;8(4). doi: 10.1523/ENEURO.0329-20.2021. Print 2021 Jul-Aug.

Abstract

The formin family member Fmn2 is a neuronally enriched cytoskeletal remodeling protein conserved across vertebrates. Recent studies have implicated Fmn2 in neurodevelopmental disorders, including sensory processing dysfunction and intellectual disability in humans. Cellular characterization of Fmn2 in primary neuronal cultures has identified its function in the regulation of cell-substrate adhesion and consequently growth cone translocation. However, the role of Fmn2 in the development of neural circuits , and its impact on associated behaviors have not been tested. Using automated analysis of behavior and systematic investigation of the associated circuitry, we uncover the role of Fmn2b in zebrafish neural circuit development. As reported in other vertebrates, the zebrafish ortholog of Fmn2 is also enriched in the developing zebrafish nervous system. We find that Fmn2b is required for the development of an excitatory interneuron pathway, the spiral fiber neuron, which is an essential circuit component in the regulation of the Mauthner cell (M-cell)-mediated acoustic startle response. Consistent with the loss of the spiral fiber neurons tracts, high-speed video recording revealed a reduction in the short latency escape events while responsiveness to the stimuli was unaffected. Taken together, this study provides evidence for a circuit-specific requirement of Fmn2b in eliciting an essential behavior in zebrafish. Our findings underscore the importance of Fmn2 in neural development across vertebrate lineages and highlight zebrafish models in understanding neurodevelopmental disorders.

摘要

formin 家族成员 Fmn2 是一种在脊椎动物中保守的富含神经元的细胞骨架重塑蛋白。最近的研究表明,Fmn2 与神经发育障碍有关,包括人类的感觉处理功能障碍和智力障碍。在原代神经元培养物中对 Fmn2 的细胞特征分析表明,它在调节细胞-基底附着以及随后的生长锥转运中发挥作用。然而,Fmn2 在神经回路发育中的作用及其对相关行为的影响尚未得到测试。我们使用行为的自动分析和相关电路的系统研究,揭示了 Fmn2b 在斑马鱼神经回路发育中的作用。如在其他脊椎动物中所报道的,Fmn2 的斑马鱼同源物也富含在发育中的斑马鱼神经系统中。我们发现 Fmn2b 是兴奋性中间神经元途径——螺旋纤维神经元发育所必需的,该神经元是调节 Mauthner 细胞(M 细胞)介导的声启动反应的重要回路组成部分。与螺旋纤维神经元束的缺失一致,高速视频记录显示短潜伏期逃避事件减少,而对刺激的反应不受影响。总之,这项研究为 Fmn2b 在诱发斑马鱼基本行为中的特定回路需求提供了证据。我们的研究结果强调了 Fmn2 在脊椎动物谱系中的神经发育中的重要性,并突出了斑马鱼模型在理解神经发育障碍中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9983/8272403/4acd37285b61/ENEURO.0329-20.2021_f001.jpg

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