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

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.