ARNT2 Acts as the Dimerization Partner of SIM1 for the Development of the Hypothalamus

Mech Dev. 2000 Feb;90(2):253-61. doi: 10.1016/s0925-4773(99)00328-7.

Abstract

One major function of the hypothalamus is to maintain homeostasis by modulating the secretion of pituitary hormones. The paraventricular (PVN) and supraoptic (SON) nuclei are major integration centers for the output of the hypothalamus to the pituitary. The bHLH-PAS transcription factor SIM1 is crucial for the development of several neuroendocrine lineages within the PVN and SON. bHLH-PAS proteins require heterodimerization for their function. ARNT, ARNT2, and BMAL1 are the three known general heterodimerization partners for bHLH-PAS proteins. Here, we provide evidence that Sim1 and Arnt2 form dimers in vitro, that they are co-expressed in the PVN and SON, and that their loss of function affects the development of the same sets of neuroendocrine cell types within the PVN and SON. Together, these results implicate ARNT2 as the in vivo dimerization partner of SIM1 in controlling the development of these neuroendocrine lineages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins*
  • Dimerization
  • Gene Expression
  • Helix-Loop-Helix Motifs*
  • Hypothalamus / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Midline Thalamic Nuclei / embryology
  • Receptors, Aryl Hydrocarbon*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Supraoptic Nucleus / embryology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • ARNTL Transcription Factors
  • Arnt protein, mouse
  • Arnt2 protein, mouse
  • Arntl protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Receptors, Aryl Hydrocarbon
  • Repressor Proteins
  • Sim1 protein, mouse
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator