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

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 nucl ear receptor, steroidogenic factor 1 (SF-1), which can be detected in the h ypothalamic primordium by Ell. Strikingly, the VMH is absent in newborn SF- 1 knockout mice, suggesting that SF-1 is essential for the development of V MH neurons. We reported previously that the VMH can be identified before it emerges as a histologically distinct nucleus (i.e., at E13) by the exclusi on of cells that are immunoreactive for both gamma-aminobutyric acid (GABA) and the synthetic enzyme, glutamic acid decarboxylase (GAD67). Subsequentl y, by E15, the developing VMH is demarcated further by cells that are immun oreactive for neuropeptide Y, estrogen receptor alpha (ER alpha), and galan in. 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 fo r neuropeptide Y, ER alpha, and galanin also are distributed aberrantly in this region. Thus, the absence of SF-1 profoundly affects the cellular arch itecture 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. J. Comp. Neurol. 423 : 579-589, 2000. (C) 2000 Wiley-Liss, Inc.