This Article Full Text Full Text (PDF) Supplemental Figures Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goshu, E. Articles by Fan, C.-M. Search for Related Content PubMed PubMed Citation Articles by Goshu, E. Articles by Fan, C.-M.

Sim2 Contributes to Neuroendocrine Hormone Gene Expression in the Anterior Hypothalamus

Department of Embryology (E.G., H.J., J.L., C.-M.F.), Carnegie Institution of Washington, Baltimore, Maryland 21210; and Research Center (J.-F.M., J.L.M.), Hôpital Sainte-Justine, Montréal, Québec, Canada H3T 1C5

Address all correspondence and requests for reprints to: Chen-Ming Fan, Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, Maryland. E-mail: fan{at}ciwemb.edu.

Paraventricular (PVN) and supraoptic nuclei of the hypothalamus maintain homeostasis by modulating pituitary hormonal output. PVN and supraoptic nuclei contain five major cell types: oxytocin-, vasopressin-, CRH-, somatostatin-, and TRH-secreting neurons. Sim1, Arnt2, and Otp genes are essential for terminal differentiation of these neurons. One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation. Here we show that Sim2, a paralog of Sim1, contributes to the expression of Trh and Ss genes in the dorsal preoptic area, anterior-periventricular nucleus, and PVN. Sim2 expression overlaps with Trh- and Ss-expressing cells, and Sim2 mutants contain reduced numbers of Trh and Ss cells. Genetically, Sim1 acts upstream of Sim2 and partially compensates for the loss of Sim2. Comparative expression studies at the anterior hypothalamus at early stages reveal that there are separate pools of Trh cells with distinctive molecular codes defined by Sim1 and Sim2 expression. Together with previous reports, our results demonstrate that Sim1 and Otp utilize two common downstream genes, Brn2 and Sim2, to mediate distinctive sets of neuroendocrine hormone gene expression.

This article has been cited by other articles:

				S. Woods, A. Farrall, C. Procko, and M. L. Whitelaw The bHLH/Per-Arnt-Sim transcription factor SIM2 regulates muscle transcript myomesin2 via a novel, non-canonical E-box sequence Nucleic Acids Res., June 1, 2008; 36(11): 3716 - 3727. [Abstract] [Full Text] [PDF]

				X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]

				O. J. Halvorsen, K. Rostad, A. M. Oyan, H. Puntervoll, T. H. Bo, L. Stordrange, S. Olsen, S. A. Haukaas, L. Hood, I. Jonassen, et al. Increased Expression of SIM2-s Protein Is a Novel Marker of Aggressive Prostate Cancer Clin. Cancer Res., February 1, 2007; 13(3): 892 - 897. [Abstract] [Full Text] [PDF]

				D. E. G. McNay, M. Pelling, S. Claxton, F. Guillemot, and S.-L. Ang Mash1 Is Required for Generic and Subtype Differentiation of Hypothalamic Neuroendocrine Cells Mol. Endocrinol., July 1, 2006; 20(7): 1623 - 1632. [Abstract] [Full Text] [PDF]

				J.-F. Marion, C. Yang, A. Caqueret, F. Boucher, and J. L. Michaud Sim1 and Sim2 are required for the correct targeting of mammillary body axons Development, December 15, 2005; 132(24): 5527 - 5537. [Abstract] [Full Text] [PDF]

				F. S. J. de Souza, A. M. Santangelo, V. Bumaschny, M. E. Avale, J. L. Smart, M. J. Low, and M. Rubinstein Identification of Neuronal Enhancers of the Proopiomelanocortin Gene by Transgenic Mouse Analysis and Phylogenetic Footprinting Mol. Cell. Biol., April 15, 2005; 25(8): 3076 - 3086. [Abstract] [Full Text] [PDF]