Involvement of SF-1 in neurogenesis and neuronal migration in the developing neocortex

• SF-1 was expressed in the dorsal telencephalon at E15.5–E18.5, but not in adulthood.
• In SF-1 KO embryos, neurons in the IZ/SVZ were increased, in the CP decreased.
• The APCs increased and radial fibers showed abnormal morphology in SF-1 KO embryos.
• Cell cycle duration was shortened and exit inhibited in SF-1 KO stem/progenitor cells.
• Expression of ESRα was up- and of Cyp19a1 down-regulated in SF-1 KO embryos.

The nuclear receptor steroidogenic factor-1 (SF-1) plays essential roles in the development and function of the endocrine and reproductive systems. During embryogenesis, SF-1 is expressed in the ventromedial hypothalamic nucleus (VMH) and regulates the migration and terminal differentiation of the VMH neurons. Additionally, in situ hybridization data indicated SF-1 expression in the dorsal telencephalon at embryonic day (E) 13.5. In this study, we investigated the neocortical development in SF-1 knockout (KO) mouse embryos. The number of neurons was increased in the intermediate/subventricular zones and decreased in the cortical plate in the SF-1 KO embryos. SF-1 KO embryos produced more neural stem/progenitor cells, especially apical progenitor cells, and showed abnormal radial glial fiber morphology. The increase in neural stem/progenitor cells was caused by an increased S-phase fraction in the proliferative cells and the inhibition of cell cycle exit in these cells. The mRNA expression of the estrogen receptor ESRα was up-regulated and that of the estrogen synthetase Cyp19a1 was down-regulated in the dorsal telencephalon of SF-1 KO embryos. We showed that SF-1 is expressed in the dorsal telencephalon at E15.5 and E18.5, but not in adult animals. Our data demonstrated that SF-1 is involved in cell cycle regulation, neurogenesis, and neuronal migration via controlling the estrogen signaling for proper neocortical development.