Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons

Title
Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons
Authors
이보라김장현안태경김상수Esha M. PatelJacob RaberSoo-Kyung Lee이승희Jae W. Lee
Issue Date
2018-05
Publisher
Nature Communications
Citation
VOL 9, NO 2026 (2018)-13
Abstract
Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear. Here we report that the transcription factors Dlx1/2 and Otp coordinate the balanced generation of the two functionally related neurons in the hypothalamic arcuate nucleus, GHRH-neurons promoting the growth and AgRP-neurons controlling the feeding and energy expenditure. Dlx1/2-deficient mice show a loss-of-GHRH-neurons and an increase of AgRP-neurons, and consistently develop dwarfism and consume less energy. These results indicate that Dlx1/2 are crucial for specifying the GHRH-neuronal identity and, simultaneously, for suppressing AgRP-neuronal fate. We further show that Otp is required for the generation of AgRP-neurons and that Dlx1/2 repress the expression of Otp by directly binding the Otp gene. Together, our study demonstrates that the identity of GHRH- and AgRP-neurons is synchronously specified and segregated by the Dlx1/2-Otp gene regulatory axis.
URI
http://pubs.kist.re.kr/handle/201004/68141
ISSN
2041-1723
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