Coordinated Actions of the Forkhead Protein Foxp1 and Hox Proteins in the Columnar Organization of Spinal Motor Neurons

Abstract

The formation of locomotor circuits depends on the spatially organized generation of motor columns that innervate distinct muscle and autonomic nervous system targets along the body axis. Within each spinal segment, multiple motor neuron classes arise from a common progenitor population; however, the mechanisms underlying their diversification remain poorly understood. Here, we show that the Forkhead domain transcription factor Foxp1 plays a critical role in defining the columnar identity of motor neurons at each axial position. Using genetic manipulations, we demonstrate that Foxp1 establishes the pattern of LIM-HD protein expression and accordingly organizes motor axon projections, their connectivity with peripheral targets, and the establishment of motor pools. These functions of Foxp1 act in accordance with the rostrocaudal pattern provided by Hox proteins along the length of the spinal cord, suggesting a model by which motor neuron diversity is achieved through the coordinated actions of Foxp1 and Hox proteins.