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Publication : ERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.

First Author  Khan MN Year  2022
Journal  PLoS Biol Volume  20
Issue  12 Pages  e3001923
PubMed ID  36542664 Mgi Jnum  J:332398
Mgi Id  MGI:7424266 Doi  10.1371/journal.pbio.3001923
Citation  Khan MN, et al. (2022) ERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control. PLoS Biol 20(12):e3001923
abstractText  The ability of terrestrial vertebrates to effectively move on land is integrally linked to the diversification of motor neurons into types that generate muscle force (alpha motor neurons) and types that modulate muscle proprioception, a task that in mammals is chiefly mediated by gamma motor neurons. The diversification of motor neurons into alpha and gamma types and their respective contributions to movement control have been firmly established in the past 7 decades, while recent studies identified gene expression signatures linked to both motor neuron types. However, the mechanisms that promote the specification of gamma motor neurons and/or their unique properties remained unaddressed. Here, we found that upon selective loss of the orphan nuclear receptors ERR2 and ERR3 (also known as ERRbeta, ERRgamma or NR3B2, NR3B3, respectively) in motor neurons in mice, morphologically distinguishable gamma motor neurons are generated but do not acquire characteristic functional properties necessary for regulating muscle proprioception, thus disrupting gait and precision movements. Complementary gain-of-function experiments in chick suggest that ERR2 and ERR3 could operate via transcriptional activation of neural activity modulators to promote a gamma motor neuron biophysical signature of low firing thresholds and high firing rates. Our work identifies a mechanism specifying gamma motor neuron functional properties essential for the regulation of proprioceptive movement control.
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