Disruption of the gene encoding SF-1 alters the distribution of hypothalamic neuronal phenotypes

Tammy L. Dellovade, Morag Young, Elizabeth P. Ross, Rachael Henderson, Kathleen Caron, Keith Parker, Stuart A. Tobet

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Abstract

The ventromedial nucleus of the hypothalamus (VMH) in mice first emerges as a histologically distinct cell cluster around embryonic day 17 (E17). The earliest known marker for cells destined to form the VMH is the orphan nuclear receptor, steroidogenic factor 1 (SF-1), which can be detected in the hypothalamic primordium by E11. Strikingly, the VMH is absent in newborn SF-1 knockout mice, suggesting that SF-1 is essential for the development of VMH neurons. We reported previously that the VMH can be identified before it emerges as a histologically distinct nucleus (i.e., at E13) by the exclusion of cells that are immunoreactive for both γ-aminobutyric acid (GABA) and the synthetic enzyme, glutamic acid decarboxylase (GAD67). Subsequently, by E15, the developing VMH is demarcated further by cells that are immunoreactive for neuropeptide Y, estrogen receptor α (ERα), and galanin. It is noteworthy that the normal exclusion of GABA from the developing VMH is not seen in SF-1 knockout mice, and cells that are immunoreactive for neuropeptide Y, ERα, and galanin also are distributed aberrantly in this region. Thus, the absence of SF-1 profoundly affects the cellular architecture of the VMH from early stages in its formation. These data suggest that, directly or indirectly, SF-1 plays important roles in determining the distribution of cells in the mediobasal hypothalamus. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)579-589
Number of pages11
JournalThe Journal of Comparative Neurology
Volume423
Issue number4
DOIs
Publication statusPublished - 7 Aug 2000
Externally publishedYes

Keywords

  • γ-aminobutyric acid
  • Estrogen receptor α
  • Glutamic acid decarboxylase
  • Steroidogenic factor 1
  • Ventromedial nucleus of the hypothalamus

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