Exploring the Role of Axial Identity on V2a Interneuron Phenotype and Function by Nicholas Elder

Nicholas Elder

UC San Francisco

My research is focused on the development and diversification of neurons within the human spinal cord. More specifically, I am focused on and excitatory population of spinal interneurons called V2a neurons which help to control motor circuits and which been shown to diversify to two subtypes. I am using human stem cells to generate V2a neurons to study how V2a subtypes are established, and whether those subtypes have functional differences.


As the spinal cord develops, many neural populations are established, each with characteristics critical for nervous system function. V2a interneurons are a key population of neurons involved in central pattern generation (CPG) and motor control within the spinal cord. Two major types of V2a neurons have been identified, which display marked shifts in their proportional abundance along the rostral-caudal axis of the mouse spinal cord, but the mechanisms that lead to this patterning remain to be molecularly described or controlled. To examine V2a neurons in vitro, I have established a lineage-traced human stem cell line based on expression of FOXN4 in V2a progenitors. My objective is to elucidate the molecular mechanisms that contribute to human V2a diversification and their impacts on neuron function. I hypothesize that axial identity, conferred by HOX transcription factors 1) regulate the generation of Type I and Type II V2a neurons though specific enhancers and 2) result in functional differences in CPG responsiveness and automaticity between axially distinct populations of V2a neurons.


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