Estrogens regulate early embryonic development of the olfactory sensory system via estrogen-responsive glia
Fri-S8-001
Presented by: Aya Takesono
Note: This presentation is for a symposium “Sex-steroid hormones in olfaction” organised by Dr. Tatjana Abaffy.
Estrogen is well-known to regulate development of sexual dimorphisms of the brain, however its role in the brain during early embryonic development prior to sex-differentiation is unclear.
Using estrogen biosensor zebrafish models, we demonstrate that estrogen activity in the embryonic brain occurs specifically in a type of glia located within the OB, which we name estrogen-responsive olfactory bulb/EROB cells. In response to estrogen, EROB cells overlay the outermost layer of the OB and interact tightly with olfactory sensory neurons at the olfactory glomeruli. Pharmacologically Inhibiting estrogen activity by an estrogen receptor antagonist, ICI182,780 (ICI), and/or EROB cell ablation impede olfactory glomerular development, including topological organisation of olfactory glomeruli and inhibitory synaptogenesis in the OB. Furthermore, activation of estrogen signalling inhibits both intrinsic and olfaction-dependent neuronal activity in the OB, whereas ICI or EROB cell ablation results in the opposite effect on neuronal excitability. Altering the estrogen signalling disrupts olfaction-mediated behaviour in later larval stage. We propose that estrogen acts on glia to regulate development of functional OB circuits, thereby modulating the local excitability in the OB and olfaction-mediated behaviour. Our data also suggest a possibility that the estrogen/EROB cascade may be an important site of action for environmental estrogens causative of neurodevelopmental impairments in animals and humans.
Estrogen is well-known to regulate development of sexual dimorphisms of the brain, however its role in the brain during early embryonic development prior to sex-differentiation is unclear.
Using estrogen biosensor zebrafish models, we demonstrate that estrogen activity in the embryonic brain occurs specifically in a type of glia located within the OB, which we name estrogen-responsive olfactory bulb/EROB cells. In response to estrogen, EROB cells overlay the outermost layer of the OB and interact tightly with olfactory sensory neurons at the olfactory glomeruli. Pharmacologically Inhibiting estrogen activity by an estrogen receptor antagonist, ICI182,780 (ICI), and/or EROB cell ablation impede olfactory glomerular development, including topological organisation of olfactory glomeruli and inhibitory synaptogenesis in the OB. Furthermore, activation of estrogen signalling inhibits both intrinsic and olfaction-dependent neuronal activity in the OB, whereas ICI or EROB cell ablation results in the opposite effect on neuronal excitability. Altering the estrogen signalling disrupts olfaction-mediated behaviour in later larval stage. We propose that estrogen acts on glia to regulate development of functional OB circuits, thereby modulating the local excitability in the OB and olfaction-mediated behaviour. Our data also suggest a possibility that the estrogen/EROB cascade may be an important site of action for environmental estrogens causative of neurodevelopmental impairments in animals and humans.