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

Author

Listed:
  • 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
    Oregon Health and Science University)

  • Soo-Kyung Lee

    (Oregon Health and Science University
    Oregon Health and Science University)

  • Seunghee Lee

    (Seoul National University)

  • Jae W. Lee

    (Oregon Health and Science University)

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.

Suggested Citation

  • Bora Lee & Janghyun Kim & Taekyeong An & Sangsoo Kim & Esha M. Patel & Jacob Raber & Soo-Kyung Lee & Seunghee Lee & Jae W. Lee, 2018. "Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04377-4
    DOI: 10.1038/s41467-018-04377-4
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