Motor Neurons with Axial Muscle Projections Specified by Wnt4/5 Signaling

Axial muscles are innervated by motor neurons of the median motor column (MMC). In contrast to the segmentally restricted motor columns that innervate limb, body wall, and neuronal targets, MMC neurons are generated along the entire length of the spinal cord. We show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate. These Wnts appear to establish a ventral(high) to dorsal(low) signaling gradient and promote MMC identity and connectivity by maintaining expression of the LIM homeodomain proteins Lhx3/4 in spinal motor neurons. Elevation of Wnt4/5 activity generates additional MMC neurons at the expense of other motor neuron columnar subtypes, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons. Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity.