Conditional Deletion of NFIA Alters Motor Neuron Development
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Conditional Deletion of NFIA Alters Motor Neuron Development

Abstract

Proper spinal cord development results in spatially organized motor columns that innervate muscles along the rostral-caudal body axis. This is achieved in large part through the concerted action of a combination of transcription factors. The transcription factor Nuclear Factor 1 A (NFIA) is a regulator of glial cell development where it is both necessary and sufficient to induce glial cell specification. NFIA is also expressed in developing neurons in the brain and in spinal motor neurons. Recently, differential expression of NFIA in spinal glial and motor neuron populations was found to depend on distinct chromatin architectures. However, the function of NFIA is motor neurons remains poorly understood. Here, we show that NFIA is expressed in all but one motor column in developing spinal motor neurons. We define NFIA expression in both chick and mouse spinal cords, finding that NFIA is expressed in MMC, HMC, LMCm, and LMCl columns. Using genetic manipulations in both chick and mouse spinal cord, we found that NFIA is not required for the initial specification of motor neuron populations. Rather, conditional deletion of NFIA in motor neurons leads to disorganization of the lateral medial motor neuron (LMC) columns. A reduction in expression and abhorrent migration of FOXP1 and LIM1/2 were observed with cells from the LMC-lateral column incorrectly migrating into the LMC-medial region. Thus, NFIA is important for maintain proper motor neuron columnar organization.

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