Dataset Information

MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords.

ABSTRACT: The precise organization of motor neuron subtypes in a columnar pattern in developing spinal cords is controlled by cross-interactions of multiple transcription factors and segmental expressions of Hox genes and their accessory proteins. Accurate expression levels and domains of these regulators are essential for organizing spinal motor neuron columns and axonal projections to target muscles. Here, we show that microRNA miR-9 is transiently expressed in a motor neuron subtype and displays overlapping expression with its target gene FoxP1. Overexpression or knockdown of miR-9 alters motor neuron subtypes, switches columnar identities, and changes axonal innervations in developing chick spinal cords. miR-9 modifies spinal columnar organization by specifically regulating FoxP1 protein levels, which in turn determine distinct motor neuron subtypes. Our findings demonstrate that miR-9 is an essential regulator of motor neuron specification and columnar formation. Moreover, the overlapping expression of miR-9 and its target FoxP1 further illuminates the importance of fine-tuning regulation by microRNAs in motor neuron development.

SUBMITTER: Otaegi G

PROVIDER: S-EPMC3040495 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords.

Otaegi Gaizka G Pollock Andrew A Hong Janet J Sun Tao T

The Journal of neuroscience : the official journal of the Society for Neuroscience 20110101 3

The precise organization of motor neuron subtypes in a columnar pattern in developing spinal cords is controlled by cross-interactions of multiple transcription factors and segmental expressions of Hox genes and their accessory proteins. Accurate expression levels and domains of these regulators are essential for organizing spinal motor neuron columns and axonal projections to target muscles. Here, we show that microRNA miR-9 is transiently expressed in a motor neuron subtype and displays overla ...[more]

PMID: 21248104

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Project description:Upper cervical spinal cord injuries (SCI) disrupt descending inputs to phrenic motor neurons (PhMNs), impairing respiratory function. Unilateral spinal hemisection at C2 (C2SH) results in loss of ipsilateral rhythmic diaphragm muscle (DIAm) EMG activity associated with lower force behaviors accomplished by recruitment of smaller PhMNs in rats. Activity during higher force, non-ventilatory behaviors that recruit larger PhMNs is minimally impaired following C2SH. We previously showed neuroplasticity in glutamatergic receptor expression in PhMN post-C2SH with changes in NMDA receptor expression reflecting functional recovery over time. We hypothesize that C2SH-induced changes in glutamatergic receptor (AMPA and NMDA) mRNA expression in PhMNs vary with motor neuron size, with more pronounced changes in smaller PhMNs. Retrogradely-labelled PhMNs were classified in tertiles according to somal surface area and mRNA expression was measured using single-cell, multiplex fluorescence in situ hybridization. Ipsilateral to C2SH, a pronounced reduction in NMDA mRNA expression in PhMNs was evident at 3 days post-injury with similar impact on PhMNs in the lower size tertile (~68% reduction) and upper tertile (~60%); by 21 days, there was near complete restoration of NMDA receptor mRNA expression across all PhMNs. There were no changes in NMDA mRNA expression contralateral to C2SH. There were no changes in AMPA mRNA expression at PhMNs on either side of the spinal cord or at any time-point post-C2SH. In summary, following C2SH there is ipsilateral reduction in PhMN NMDA mRNA expression at 3 days that is not limited to smaller PhMN recruited in the generation of lower force ventilatory behaviors. The recovery of NMDA mRNA expression by 21 days post-C2SH is consistent with evidence of spontaneous recovery of ipsilateral DIAm activity at this timepoint. These findings suggest a possible role for NMDA receptor mediated glutamatergic signaling in mechanisms supporting postsynaptic neuroplasticity at the PhMN pool and recovery of DIAm activity after cervical SCI.

Dataset Information

MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords.

Publications

MicroRNA miR-9 modifies motor neuron columns by a tuning regulation of FoxP1 levels in developing spinal cords.

Similar Datasets

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