Loss of steroidogenic factor 1 alters cellular topography in the mouse ventromedial nucleus of the hypothalamus

Aline M. Davis, Marianne L. Seney, Nancy R. Stallings, Liping Zhao, Keith L. Parker, Stuart A. Tobet

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1) exhibit marked structural abnormalities of the ventromedial nucleus of the hypothalamus (VMH). In this study, we sought to determine the molecular mechanisms underlying the VMH abnormalities. To trace SF-1-expressing neurons, we used a SF-1/enhanced green fluorescent protein (eGFP) transgene. Although the total numbers of eGFP-positive cells in wild-type (WT) and SF-1 KO mice were indistinguishable, cells that normally localize precisely within the VMH were scattered more diffusely in adjacent regions in SF-1 KO mice. This abnormal distribution is likely due to the loss of SF-1 expression in VMH neurons rather than secondary effects of deficient steroidogenesis, as redistribution also was seen in mice with a CNS-specific KO of SF-1. Thus, the absence of SF-1 alters the distribution of cells that normally form the VMH within the mediobasal hypothalamus. Consistent with this model, the hypothalamic expression patterns of the transcription factors islet-1 and nkx2.1 also were displaced in SF-1 KO mice. Independent of gene expression, birthdate analyses further suggested that cells with earlier birthdates were affected more severely by the loss of SF-1 than were later born cells. We conclude that the absence of SF-1 causes major changes in cellular arrangement within and around the developing VMH that result from altered cell migration.

Original languageEnglish (US)
Pages (from-to)424-436
Number of pages13
JournalJournal of Neurobiology
Volume60
Issue number4
DOIs
StatePublished - Sep 15 2004

Keywords

  • Neuronal migration
  • Orphan nuclear receptor
  • SF-1
  • VMH
  • eGFP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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    Davis, A. M., Seney, M. L., Stallings, N. R., Zhao, L., Parker, K. L., & Tobet, S. A. (2004). Loss of steroidogenic factor 1 alters cellular topography in the mouse ventromedial nucleus of the hypothalamus. Journal of Neurobiology, 60(4), 424-436. https://doi.org/10.1002/neu.20030