Functional sub-classification of genetically identified interneurons in the spinal cord

生物学中最基本的问题之一是脊椎动物的神经系统是如何发育的。我的研究项目侧重于了解脊髓神经元功能群形成的基础发育过程。胚胎脊髓中不同的祖细胞结构域产生运动神经元（MN）和不同类别的中间神经元，每种都具有不同的分子特征。 虽然这些组中的细胞来自单一的祖细胞结构域，但它们后来可能发育成异质群体。最近的研究揭示了调节有丝分裂后MN和V2中间神经元细分的分子程序，尽管对其他脊髓中间神经元群体的这一过程知之甚少。甚至更少的是知道这些神经元群，这是在胚胎发育过程中定义的出生后成熟过程。我们的实验室将使用一个特殊的组，V3中间神经元，作为一个模型系统来研究脊髓中间神经元的细分。V3中间神经元产生于最腹侧的前体结构域，p3，并在有丝分裂早期表达Sim 1转录因子。 虽然所有的V3神经元都是突触能和连合的，但我们发现这些细胞后来迁移到脊髓内的不同位置，在那里它们显示出不同的生理和解剖特性，表明存在不同的V3亚类。我假设，V3神经元分化成不同的亚群，当他们迁移到不同的位置在一个特定的部分，在那里他们的发展是由转录因子网络。 本研究的具体目标是：（1）系统地研究V3神经元亚群的内在电生理特性、定位和形态学特征;（2）利用微阵列分析技术研究控制V3神经元亚群分化的分子因素;（3）研究出生后V3神经元亚群的电生理特征变化。我们的研究将描述特定神经元群体的发育和模式，并促进我们对脊髓中神经回路如何组织的理解。

One of the most fundamental questions in biology is how the vertebrate nervous system develops. My research program focuses on understanding developmental processes underlying the formation of functional groups of spinal cord neurons. Different progenitor domains in the embryonic spinal cord give raise to motor neurons (MNs) and different classes of interneurons, each with a distinct molecular profile. Although cells within those groups arise from a single progenitor domain, they may later develop into heterogeneous populations. Recent studies have revealed the molecular programs that regulate subdivision of postmitotic MNs and V2 interneurons, although little is known about this process in other spinal interneuron populations. Even less is known about the postnatal maturation process of these neuron groups, which are defined during embryogenesis. Our lab will use a particular group, V3 interneurons, as a model system to study the subdivision of spinal interneurons. V3 interneurons arise from the most ventral progenitor domain, the p3, and express the Sim1 transcription factor at an early postmitotic stage. While all V3 neurons are glutamatergic and commissural, we have discovered that these cells later migrate to different locations within the spinal cord where they display divergent physiological and anatomical properties, indicating the existence of different V3 subclasses. I hypothesize that V3 neurons differentiate into different subpopulations when they migrate into different positions at a specific segment, where their development is governed by transcription factor networks. The specific objectives I will achieve with this proposal are: (1) to systematically characterize functional V3 subgroups according to their intrinsic electrophysiological properties, localization and morphology; (2) to profile the molecular factors that control the subdivision of V3 neurons using microarray analyses; (3) to investigate the changes of eletrophysiological features of these subgroups of V3 neurons during postnatal stages. Our study will characterize the development and patterning of a specific neuronal population and facilitate our understanding of how neural circuits are organized in the spinal cord.