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

Bora Lee, Janghyun Kim, Taekyeong An, Sangsoo Kim, Esha M. Patel, Jacob Raber, Soo-Kyung Lee, Seunghee Lee () and Jae W. Lee ()
Additional contact information
Bora Lee: Korea Institute of Science and Technology (KIST)
Janghyun Kim: Oregon Health and Science University
Taekyeong An: Soongsil University
Sangsoo Kim: Soongsil University
Esha M. Patel: Oregon Health and Science University
Jacob Raber: Oregon Health and Science University
Soo-Kyung Lee: Oregon Health and Science University
Seunghee Lee: Seoul National University
Jae W. Lee: Oregon Health and Science University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04377-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04377-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04377-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().