Abstract

BackgroundNeuronal topographic map formation requires appropriate selection of axonal trajectories at intermediate choice points prior to target innervation. Axons of neurons in the spinal cord lateral motor column (LMC), as defined by a transcription factor code, are thought to innervate limb target tissues exclusively. Axons of the medial and lateral LMC divisions appear to execute a binary decision at the base of the limb as they choose between ventral and dorsal limb trajectories. The cellular logic that guides motor axon trajectory choices into non-limb tissues such as the ventral flank remains unclear.ResultsWe determined the spinal cord motor column origin of motor nerves that innervate ventral flank tissues at hindlimb level. We found unexpectedly that a subset of medial LMC axons innervates ventral non-limb mesenchyme at hindlimb level, rather than entering ventral limb mesenchyme. We also found that in a conditional BmprIa mutant where all ventral hindlimb mesenchyme is converted to a dorsal identity, all medial LMC axons are redirected into the ventral flank, while lateral LMC axons innervate the bidorsal limb.ConclusionWe have found that medial LMC neurons innervate both ventral flank and limb targets. While normally only a subset of medial LMC axons innervate the flank, all are capable of doing so. Furthermore, LMC axons execute a ternary, rather than binary, choice at the base of the limb between ventral flank, ventral limb and dorsal limb trajectories. When making this choice, medial and lateral LMC axons exhibit different and asymmetric relative preferences for these three trajectories. These data redefine the LMC as a motor column that innervates both limb and body tissues.

Highlights

  • Neuronal topographic map formation requires appropriate selection of axonal trajectories at intermediate choice points prior to target innervation

  • Medial lateral motor column (LMC) axons project to the ventral flank mesenchyme To determine the columnar identity of the motor neurons whose axons project into the ventral flank at hindlimb axial levels, we retrogradely labeled these neurons by horseradish peroxidase (HRP) or lysinated tetramethylrhodamine dextran (RDA) injection [24] into ventral flank mesenchyme of E13.5 mouse embryos (Figure 1)

  • The ventral flank nerves are composed of motor axons that originate from medial LMC neurons

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Summary

Introduction

Neuronal topographic map formation requires appropriate selection of axonal trajectories at intermediate choice points prior to target innervation. Axons of neurons in the spinal cord lateral motor column (LMC), as defined by a transcription factor code, are thought to innervate limb target tissues exclusively. The precision of neural circuits requires stereotypic patterns of neuronal connectivity, which are often organized as topographic maps. The motor neurons are organized mediolaterally into medial and lateral motor columns (MMC and LMC) and their divisions. The motor columns are further subdivided into pools, and each motor pool innervates an individual muscle [3] These descriptions are generally accurate, possibly incomplete, as the identity of motor neurons that innervate many muscles, outside of the limb, has not been examined in detail

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