Cellular and transcriptomic programs linking amygdala progenitors to mature neuronal identity

项目摘要 驱动胚胎大脑发育的复杂细胞和分子事件正在变得更好 明白然而，这些早期过程如何以及在多大程度上与后来的 神经元的身份和电路的具体模式的神经元布线控制不同的行为仍然存在 未知杏仁核内侧亚核（MeA）是杏仁核发育的中枢， 处理嗅觉线索的先天（非学习）的社会行为至关重要，这表明一个直接的联系， 胚胎模式和后来的亚型神经元身份，输出连接的谱系特异性模式， 先天行为调节利用研究MeA的优势， 系统，我们提出的研究的目标是阐明细胞和分子机制，桥梁 胚胎期大脑发育，后期功能输出。根据我们以前的数据，我们假设， MeA神经元亚型身份和子电路布线模式的成熟特性是 通过细胞和分子序列预先配置，这些序列随着VZ/SVZ中的谱系分歧而展开。我们 我建议通过以下方法来检验这一假设：早期MeA谱系的细胞机制 多样化（具体目标1）和2）连接新兴的胚胎转录组计划与 获得神经元身份和电路组装和连接的遗传标识符（具体目标2）。 这将通过结合海达尔实验室在细胞和转录组机制方面的专业知识来实现 早期祖细胞特化和科尔宾实验室在杏仁核发育和功能的遗传基础。 我们建议利用创新的方法，包括子宫内超声精确引导标记MeA 祖细胞池，多光子成像，以跟踪神经元，因为他们出现，和尖端的无监督 单核（sn）RNA-seq鉴定作为MeA的细胞和分子因子的全部库 祖细胞产生功能连接的出生后神经元。

Project Summary The complex cellular and molecular events driving embryonic brain development are becoming better understood. However, how and to what extent these early processes are linked to the later emergence of neuronal identity and circuit specific patterns of neuronal wiring controlling diverse behaviors remains unknown. Our previous studies of development of medial subnucleus of the amygdala (MeA), a central hub for processing olfactory cues essential for innate (unlearned) social behavior, suggests a direct link between embryonic patterning and later subtype neuronal identity, lineage-specific patterns of output connectivity and innate behavioral regulation. Leveraging the advantages of studying the MeA, a developmentally hard-wired system, the goal of our proposed studies is elucidate the cellular and molecular mechanisms that bridge embryonic brain development with later functional outputs. Based on our previous data, we hypothesize that the mature properties of MeA neuronal subtype identity and subcircuit wiring patterns are preconfigured via cellular and molecular sequalae that unfold as lineages diverge in the VZ/SVZ. We propose to test this hypothesis by determining: the cellular mechanisms underlying early MeA lineage diversification (Specific Aim 1) and 2) linking emerging embryonic transcriptomic programs with the acquisition of genetic identifiers of neuronal identity and circuit assembly and connectivity (Specific Aim 2). This will be achieved by combining the expertise of the Haydar lab in cellular and transcriptomic mechanisms of early progenitor specification and the Corbin lab in the genetic basis of amygdala development and function. We propose to utilize innovative approaches including in utero ultrasound precision guided labeling of MeA progenitor pools, multiphoton imaging to follow neurons as they emerge, and cutting-edge unsupervised single-nuclei (sn) RNA-seq to identify the full repertoire of cellular and molecular factors operating as MeA progenitors generate functionally connected postnatal neurons.