title: ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus.
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.
authors.affiliation: Service de Génétique Médicale, Hôpital Sainte-Justine, Montréal, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Michaud
authors.forename: C
authors.initials: C
authors.lastname: DeRossi
authors.forename: N R
authors.initials: NR
authors.lastname: May
authors.forename: B C
authors.initials: BC
authors.lastname: Holdener
authors.forename: C M
authors.initials: CM
authors.lastname: Fan
mesh_terms: D056930:ARNTL Transcription Factors; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D019281:Dimerization; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D007031:Hypothalamus / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020644:Midline Thalamic Nuclei / Q000196:embryology; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D014157:Transcription Factors; C497397:Arnt protein, mouse; C099817:Arnt2 protein, mouse; C538961:Bmal1 protein, mouse; C101750:Sim1 protein, mouse