Lee, Bora Kim, Janghyun An, Taekyeong Kim, Sangsoo Patel, Esha M. Raber, Jacob Lee, Soo-Kyung Lee, Seunghee Lee, Jae W. 2024-01-19T22:34:51Z 2024-01-19T22:34:51Z 2021-09-03 2018-05 2041-1723 https://pubs.kist.re.kr/handle/201004/121396 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. English Nature Publishing Group Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons Article 10.1038/s41467-018-04377-4 1 Nature Communications, v.9 Nature Communications 9 Y scie scopus 000432792100002 2-s2.0-85047529530 Multidisciplinary Sciences Science & Technology - Other Topics Article ARCUATE NUCLEUS TRANSCRIPTION FACTORS DOPAMINERGIC-NEURONS HOMEOBOX FACTOR MOUSE EXPRESSION GROWTH MICE GENE DIFFERENTIATION