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Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits
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Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits
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Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits
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Journal Article
Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits
2020
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 38/71
/ 38/91
/ 64/110
/ Animals
/ Embryos
/ Gene Expression Regulation, Developmental
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ Mice
/ Neonates
/ Neurons
/ Onecut Transcription Factors - genetics
/ Onecut Transcription Factors - metabolism
/ RNA
/ Science
/ Transcription Factors - genetics
