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

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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. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 424–436, 2004