TY  - JOUR
AU  - Khan, Mudassar N
AU  - Cherukuri, Pitchaiah
AU  - Negro, Francesco
AU  - Rajput, Ashish
AU  - Fabrowski, Piotr
AU  - Bansal, Vikas
AU  - Lancelin, Camille
AU  - Lee, Tsung-I
AU  - Bian, Yehan
AU  - Mayer, William P
AU  - Akay, Turgay
AU  - Müller, Daniel
AU  - Bonn, Stefan
AU  - Farina, Dario
AU  - Marquardt, Till
TI  - ERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.
JO  - PLoS biology
VL  - 20
IS  - 12
SN  - 1544-9173
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2023-00056
SP  - e3001923
PY  - 2022
AB  - 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 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.
KW  - Animals
KW  - Mice
KW  - Motor Neurons, Gamma: physiology
KW  - Movement
KW  - Muscles
KW  - Proprioception
KW  - Receptors, Estrogen: metabolism
KW  - Esrrb protein, mouse (NLM Chemicals)
KW  - Receptors, Estrogen (NLM Chemicals)
KW  - Esrrg protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9815657
C6  - pmid:36542664
DO  - DOI:10.1371/journal.pbio.3001923
UR  - https://pub.dzne.de/record/169177
ER  -