biostudies-literatureKhan MNEuropean Research Council under the European Union's Seventh Framework ProgrammeEuropean Research Council through the Synergy Grant NaturalBionicSDeutsche ForschungsgemeinschaftBMBF IDSNDFG Cluster of Excellence 171 for Nanoscale Microscopy and Molecular Physiology of the BrainEuropean Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-CurieERA-Net E-Rare MAXOMODCollaborative Research Centers (CRC) DFGe3001923https://www.ebi.ac.uk/biostudies/studies/S-EPMC9815657biostudies-literatureUnknown20(12)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 EPLoS biologyERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.PMC9815657702491810346368482240/GRK2416CRC 1286/Z2311710-MU TUNINGKhan MNBansal VLee TIMarquardt TRajput AAkay TFabrowski PBonn SNegro FMayer WPCherukuri PBian YMuller DLancelin CFarina DfalseERR2 and ERR3 promote the development of gamma motor neuron functional properties required for proprioceptive movement control.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 E2022-01-01T00:00:00Z2022 Dec2025-04-22T04:30:57.074Z2025-04-05T21:00:43.564ZS-EPMC98156573654266410.1371/journal.pbio.3001923