Abstract
SummaryAxial 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 ventralhigh to dorsallow 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.
Highlights
Motor behaviors depend on the coordinate recruitment of different muscle groups, each activated by a specialized set of motor neurons
Elevation of Wnt4/5 activity results in the generation of additional median motor column (MMC) neurons, at the expense of hypaxial motor column (HMC) and lateral motor column (LMC) neurons, whereas depletion of Wnt4/5 activity inhibits the production of MMC neurons and generates additional HMC neurons
Our findings show that motor neuron generation in the spinal cord depends on two dorsoventral signaling systems—mediated by Sonic hedgehog (Shh) and Wnt4/5 proteins—and that the concerted activity of these two systems establishes an early divergence in motor neuron columnar identity
Summary
Motor behaviors depend on the coordinate recruitment of different muscle groups, each activated by a specialized set of motor neurons. The early specification of spinal motor neuron fate is initiated by a dorsoventral gradient of Sonic hedgehog (Shh) signaling activity (Jessell, 2000), which induces the sequential expression of a series of homeodomain (HD) transcription factors, notably the Nkx6.1/.2, Mnr2/Hb9, Lhx3/4, and Isl1/2 proteins, in ventral progenitors and postmitotic motor neurons (Dessaud et al, 2008). This dorsoventral signaling program operates along the entire length of the spinal cord, ensuring that motor neurons are produced at all segmental levels (Jessell, 2000)
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