NSF Postdoctoral Fellowship in Biology FY 2021: Defining the role of ZEB2 in the development of convergent neural circuitry for vocal imitation

2021 财年 NSF 生物学博士后奖学金：定义 ZEB2 在声音模仿汇聚神经回路发展中的作用

• 批准号: 2109691
• 负责人: Gregory Gedman
• 金额: $ 13.8万
• 依托单位: Gedman, Gregory Louis
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2109691&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; FY

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Vocal imitation is thought to have evolved convergently in songbirds, parrots, and humans because, despite not sharing a common ancestor with this trait, these three groups exhibit similar brain pathways for the production of learned song and speech. The genetic drivers that shape these shared brain pathways and behaviors are not known. Recent cross-species comparisons implicate ZEB2 as a gene important for forming these brain pathways, including that ZEB2 mutations result in impaired speech production in humans. This project aims to understand the role of ZEB2 in the development and function of vocal imitation brain pathways in songbirds and parrots and to relate these findings to humans. Broader impacts include enhancing participation of underrepresented minority students in STEM through a workshop on bioinformatics. In order to test the necessity of ZEB2 for the formation of convergent vocal imitation neural circuitry in songbirds and parrots, the project aims to 1) assess behavioral outcomes following expression manipulation in specific brain regions and 2) define the transcriptomic and chromatin modifications associated with expression manipulation in both species. The Fellow will use RNAi-mediated viral expression vectors to knockdown ZEB2 in songbird HVC (high vocal center) and parrot NLC (central nucleus of the lateral nidopallium), two important premotor analogs shown to control the timing of learned vocalizations in birds. This manipulation will be introduced early in development prior to the formation of the specialized vocal imitation connectivity to test ZEB2’s role in this process. Transcriptomic profiling will be performed to determine the downstream target genes impacted in both species. The Fellow will also profile the regulatory landscape of the ZEB2 transcription factor in both species using ChIP-Seq analysis for chromatin accessibility in these brain regions and adjacent non-vocal imitation regions, highlighting important molecular pathways for vocal imitation. In sum, this project will offer important insights into the constraints on the genome for the convergent evolution of complex behaviors across taxa while offering dozens of new candidate genes for future study. The Fellow will develop expertise in neuroscience, in vivo gene manipulation, and genomic sequencing and will teach a R-based bioinformatics workshop through the RISE program at NMSU.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这一行动为NSF 2021财年生物学博士后研究奖学金提供了资金，综合研究调查了支配基因组、环境和表型之间相互作用的生命规则。该奖学金支持研究员的研究和培训，这些研究员将以创新的方式为生活规则领域做出贡献。声音模仿被认为是在鸣禽、鹦鹉和人类中一致进化的，因为尽管这三个群体没有共同的祖先具有这一特征，但这三个群体在产生习得的歌曲和语音方面表现出相似的大脑路径。塑造这些共享的大脑路径和行为的遗传驱动因素尚不清楚。最近的跨物种比较表明，ZEB2是形成这些大脑通路的重要基因，包括ZEB2突变导致人类语音产生障碍。该项目旨在了解ZEB2在鸣禽和鹦鹉发声模拟脑通路的发育和功能中的作用，并将这些发现与人类联系起来。更广泛的影响包括通过生物信息学讲习班加强代表不足的少数族裔学生对STEM的参与。为了测试ZEB2在鸣禽和鹦鹉形成收敛的发声模仿神经回路中的必要性，该项目旨在1)评估在特定大脑区域进行表达操纵后的行为结果，2)确定与这两个物种的表达操纵相关的转录和染色质修饰。这位研究员将使用RNAi介导的病毒表达载体在鸣禽HVC(高声中心)和鹦鹉NLC(外侧nidopallium中央核)中敲除ZEB2，这两个重要的运动前类似物被证明控制鸟类学习发声的时间。这种操作将在开发的早期引入，然后形成专门的发声模仿连接，以测试ZEB2的S在这一过程中的作用。将进行转录图谱分析，以确定在两个物种中受影响的下游目标基因。这位研究员还将使用CHIP-SEQ分析这些大脑区域和邻近的非发声模仿区域中染色质的可及性，描述这两个物种中ZEB2转录因子的调控格局，强调发声模仿的重要分子途径。总而言之，该项目将为基因组上复杂行为跨类群的收敛进化提供重要的见解，同时为未来的研究提供数十个新的候选基因。该研究员将开发神经科学、体内基因操作和基因组测序方面的专业知识，并将通过NMSU的RISE计划教授基于R的生物信息学研讨会。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。