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理解脊髓神经元功能群形成的发育过程。胚胎脊髓中不同的祖结构域产生运动神经元（MNs）和不同种类的中间神经元，每一种神经元都具有不同的分子特征。虽然这些群体中的细胞起源于单一祖域，但它们后来可能发展成异质群体。最近的研究揭示了调节有丝分裂后MNs和V2中间神经元的分子程序，尽管对其他脊髓中间神经元群体的这一过程知之甚少。这些神经元群是在胚胎发生过程中确定的，对其出生后的成熟过程所知甚少。本实验室将以V3中间神经元为模型系统，研究脊髓中间神经元的细分。V3中间神经元起源于最腹侧的前祖结构域p3，并在有丝分裂后早期表达Sim1转录因子。虽然所有V3神经元都是谷氨酸能和互交的，但我们发现这些细胞后来迁移到脊髓内的不同位置，在那里它们表现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神经元在迁移到特定片段的不同位置时分化为不同的亚群，其中它们的发育受转录因子网络的控制。我将通过本提案实现的具体目标是：(1)根据其固有的电生理特性，定位和形态系统地表征功能V3亚群；(2)利用微阵列分析分析控制V3神经元细分的分子因素；(3)观察这些V3神经元亚群在出生后的电生理特征变化。我们的研究将描述特定神经元群的发育和模式，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.