Dataset Information

Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation.

ABSTRACT: Many networks throughout the nervous system are organized into topographic maps, where the positions of neuron cell bodies in the projecting field correspond with the positions of their axons in the target field. Previous studies of topographic map development show evidence for spatial patterning mechanisms, in which molecular determinants expressed across the projecting and target fields are matched directly in a point-to-point mapping process. Here, we describe a novel temporal mechanism of topographic map formation that depends on spatially regulated differences in the timing of axon outgrowth and functions in parallel with spatial point-to-point mapping mechanisms. We focus on the vagus motor neurons, which are topographically arranged in both mammals and fish. We show that cell position along the anterior-posterior axis of hindbrain rhombomere 8 determines expression of hox5 genes, which are expressed in posterior, but not anterior, vagus motor neurons. Using live imaging and transplantation in zebrafish embryos, we additionally reveal that axon initiation is delayed in posterior vagus motor neurons independent of neuron birth time. We show that hox5 expression directs topographic mapping without affecting time of axon outgrowth and that time of axon outgrowth directs topographic mapping without affecting hox5 expression. The vagus motor neuron topographic map is therefore determined by two mechanisms that act in parallel: a hox5-dependent spatial mechanism akin to classic mechanisms of topographic map formation and a novel axon outgrowth-dependent temporal mechanism in which time of axon formation is spatially regulated to direct axon targeting.

SUBMITTER: Barsh GR

PROVIDER: S-EPMC5755714 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation.

Barsh Gabrielle R GR Isabella Adam J AJ Moens Cecilia B CB

Current biology : CB 20171207 24

Many networks throughout the nervous system are organized into topographic maps, where the positions of neuron cell bodies in the projecting field correspond with the positions of their axons in the target field. Previous studies of topographic map development show evidence for spatial patterning mechanisms, in which molecular determinants expressed across the projecting and target fields are matched directly in a point-to-point mapping process. Here, we describe a novel temporal mechanism of to ...[more]

PMID: 29225029

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Project description:The axon initial segment (AIS) generates action potentials and maintains neuronal polarity by regulating the differential trafficking and distribution of proteins, transport vesicles, and organelles. Injury and disease can disrupt the AIS, and the subsequent loss of clustered ion channels and polarity mechanisms may alter neuronal excitability and function. However, the impact of AIS disruption on axon regeneration after injury is unknown. We generated male and female mice with AIS-deficient multipolar motor neurons by deleting AnkyrinG, the master scaffolding protein required for AIS assembly and maintenance. We found that after nerve crush, neuromuscular junction reinnervation was significantly delayed in AIS-deficient motor neurons compared with control mice. In contrast, loss of AnkyrinG from pseudo-unipolar sensory neurons did not impair axon regeneration into the intraepidermal nerve fiber layer. Even after AIS-deficient motor neurons reinnervated the neuromuscular junction, they failed to functionally recover because of reduced synaptic vesicle protein 2 at presynaptic terminals. In addition, mRNA trafficking was disrupted in AIS-deficient axons. Our results show that, after nerve injury, an intact AIS is essential for efficient regeneration and functional recovery of axons in multipolar motor neurons. Our results also suggest that loss of polarity in AIS-deficient motor neurons impairs the delivery of axonal proteins, mRNAs, and other cargoes necessary for regeneration. Thus, therapeutic strategies for axon regeneration must consider preservation or reassembly of the AIS.SIGNIFICANCE STATEMENT Disruption of the axon initial segment is a common event after nervous system injury. For multipolar motor neurons, we show that axon initial segments are essential for axon regeneration and functional recovery after injury. Our results may help explain injuries where axon regeneration fails, and suggest strategies to promote more efficient axon regeneration.

Dataset Information

Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation.

Publications

Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation.

Similar Datasets

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