Estrogen receptor (ER)β knockout mice reveal a role for ERβ in migration of cortical neurons in the developing brain

The present study stems from our previous observations that the brains of adult estrogen receptor β knockout (ERβ−/−) mice show regional neuronal hypocellularity especially in the cerebral cortex. We now show that ERβ is necessary for late embryonic development of the brain and is involved in both neuronal migration and apoptosis. At embryonic day (E)18.5, ERβ−/− mouse brains were smaller than those of the wild-type (WT) littermates, and there were fewer neurons in the cortex. There were no differences in size or cellularity at E14.5. When proliferating cells were labeled with 5′-bromodeoxyuridine (BrdUrd) on E12.5, a time when cortical neurogenesis in mice begins, and examined on E14.5, there was no difference between WT and ERβ−/− mice in the number of labeled cells in the cortex. However, when BrdUrd was administered between E14.5 and E16.5, a time when postmitotic neurons migrate to layers of the cortex, there were fewer BrdUrd-labeled cells in the superficial cortical layers by E18.5 and postnatal day 14 in mice lacking ERβ. At E18.5, there were more apoptotic cells in the ventricular zone of mice lacking ERβ. In addition, the processes of the cortical radial glia, which are essential for guiding the migrating neurons, were fragmented. These findings suggest that by influencing migration and neuronal survival, ERβ has an important role in brain development.