Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons

Phu V. Tran, Martin B. Lee, Oscar Marín, Baoji Xu, Kevin R. Jones, Louis F. Reichardt, John R. Rubenstein, Holly A. Ingraham

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

The ventromedial hypothalamic nucleus (VMN) is known to mediate autonomic responses in feeding and reproductive behaviors. To date, the most definitive molecular marker for the VMN is the orphan nuclear receptor steroidogenic factor-1 (SF-1). However, it is unclear whether SF-1 functions in the VMN as it does in peripheral endocrine organ development where loss of SF-1 results in organ agenesis due to apoptosis. Here, we provide evidence that SF-1 has a distinct role in later stages of VMN development by demonstrating the persistence of VMN precursors, the misexpression of an early marker (NKX2-1) concomitant with the absence of a late marker (BDNF neurotrophin), and the complete loss of projections to the bed nucleus of stria terminalis and the amygdala in sf-1 null mice. Our findings demonstrate that SF-1 is required for terminal differentiation of the VMN and suggest that transcriptional targets of SF-1 mediate normal circuitry between the hypothalamus and limbic structures in the telencephalon.

Original languageEnglish (US)
Pages (from-to)441-453
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume22
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Bibliographical note

Funding Information:
We wish to thank Dr. Ken Morohashi (Okazaki, Japan) for his generosity in providing the SF-1 antisera and Drs. M. Dallman and U. Greishammer for advice on technical aspects of this project, and members of the Ingraham lab, especially M. Bland, for meaningful discussions and review of the manuscript. This study was supported by an NRSA F32HD41327 (to P.V.T.), the National University of Singapore Scholarship (to M.B.-H.L), and research grants from: Nina Ireland, NIDA (R01DA12462), and NIMH K02 MH01046-01 (to J.R.R.), NARSAD Young Investigator Award and MIND Institute (to O.M.), and HHMI and NIH-NS P01-16033 (to L.F.R., an investigator of the Howard Hughes Medical Institute), and the UCSF Sandler Award for Basic Research, Brook Byers Award, and NICHD RO1 support (to H.A.I.).

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