Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 01 2020
22 01 2020
Historique:
received:
06
09
2019
accepted:
09
01
2020
entrez:
24
1
2020
pubmed:
24
1
2020
medline:
20
11
2020
Statut:
epublish
Résumé
In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors.
Identifiants
pubmed: 31969659
doi: 10.1038/s41598-020-57945-4
pii: 10.1038/s41598-020-57945-4
pmc: PMC6976625
doi:
Substances chimiques
Homeodomain Proteins
0
Nkx6-2 protein, mouse
0
Onecut Transcription Factors
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
996Subventions
Organisme : NEI NIH HHS
ID : R01 EY029705
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS102678
Pays : United States
Commentaires et corrections
Type : ErratumIn
Références
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