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Ex Utero Electroporation and Organotypic Slice Cultures of Embryonic Mouse Brains for Live-Imaging of Migrating GABAergic Interneurons
Published on: April 20, 2018
Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing
Ling Wang1, Sandra Andersson, Margaret Warner
1Departments of Medical Nutrition and Biosciences, NOVUM, S-141 86 Huddinge, Sweden.
Abstract:
The present study stems from our previous observations that the brains of adult estrogen receptor beta knockout (ERbeta-/-) mice show regional neuronal hypocellularity especially in the cerebral cortex. We now show that ERbeta is necessary for late embryonic development of the brain and is involved in both neuronal migration and apoptosis. At embryonic day (E)18.5, ERbeta-/- 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 ERbeta-/- 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 ERbeta. At E18.5, there were more apoptotic cells in the ventricular zone of mice lacking ERbeta. 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, ERbeta has an important role in brain development.
Insights
Estrogen receptor beta (ERbeta) is crucial for late embryonic brain development in mice. Its absence impairs neuronal migration and survival, leading to smaller brains and reduced cortical neurons.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Previous studies noted regional neuronal hypocellularity in adult estrogen receptor beta knockout (ERbeta-/-) mouse brains, particularly the cerebral cortex.
- Estrogen receptor beta (ERbeta) plays a role in adult brain function, but its role in embryonic brain development was unclear.
Purpose of the Study:
- To investigate the role of ERbeta in late embryonic brain development.
- To determine if ERbeta influences neuronal migration and apoptosis during brain formation.
Main Methods:
- Comparative analysis of wild-type (WT) and ERbeta-/- mouse brains at embryonic day (E)14.5 and E18.5.
- Cell proliferation labeling using 5'-bromodeoxyuridine (BrdUrd) at different embryonic stages (E12.5 and E14.5-E16.5).
- Assessment of neuronal migration, apoptosis, and radial glial cell morphology.
Main Results:
- ERbeta-/- mouse brains were smaller with fewer cortical neurons at E18.5, but not E14.5.
- Reduced BrdUrd-labeled cells in superficial cortical layers of ERbeta-/- mice when labeling occurred during neuronal migration (E14.5-E16.5).
- Increased apoptotic cells in the ventricular zone and fragmented radial glia processes were observed in ERbeta-/- mice at E18.5.
Conclusions:
- Estrogen receptor beta (ERbeta) is essential for normal late embryonic brain development in mice.
- ERbeta influences neuronal migration to cortical layers and promotes neuronal survival.
- Disruption of ERbeta signaling impacts the structural integrity of radial glia, affecting neuronal guidance.
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