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000169177 1001_ $$00000-0001-6231-7837$$aKhan, Mudassar N$$b0
000169177 245__ $$aERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.
000169177 260__ $$aLawrence, KS$$bPLoS$$c2022
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000169177 520__ $$aThe 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 ERRβ, ERRγ 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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000169177 650_2 $$2MeSH$$aAnimals
000169177 650_2 $$2MeSH$$aMice
000169177 650_2 $$2MeSH$$aMotor Neurons, Gamma: physiology
000169177 650_2 $$2MeSH$$aMovement
000169177 650_2 $$2MeSH$$aMuscles
000169177 650_2 $$2MeSH$$aProprioception
000169177 650_2 $$2MeSH$$aReceptors, Estrogen: metabolism
000169177 650_7 $$2NLM Chemicals$$aEsrrb protein, mouse
000169177 650_7 $$2NLM Chemicals$$aReceptors, Estrogen
000169177 650_7 $$2NLM Chemicals$$aEsrrg protein, mouse
000169177 7001_ $$aCherukuri, Pitchaiah$$b1
000169177 7001_ $$aNegro, Francesco$$b2
000169177 7001_ $$0P:(DE-2719)2811012$$aRajput, Ashish$$b3$$udzne
000169177 7001_ $$aFabrowski, Piotr$$b4
000169177 7001_ $$0P:(DE-2719)2812055$$aBansal, Vikas$$b5$$udzne
000169177 7001_ $$aLancelin, Camille$$b6
000169177 7001_ $$aLee, Tsung-I$$b7
000169177 7001_ $$aBian, Yehan$$b8
000169177 7001_ $$aMayer, William P$$b9
000169177 7001_ $$aAkay, Turgay$$b10
000169177 7001_ $$0P:(DE-2719)2811675$$aMüller, Daniel$$b11$$udzne
000169177 7001_ $$0P:(DE-2719)2810547$$aBonn, Stefan$$b12$$udzne
000169177 7001_ $$aFarina, Dario$$b13
000169177 7001_ $$aMarquardt, Till$$b14
000169177 773__ $$0PERI:(DE-600)2126773-X$$a10.1371/journal.pbio.3001923$$gVol. 20, no. 12, p. e3001923 -$$n12$$pe3001923$$tPLoS biology$$v20$$x1544-9173$$y2022
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