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Ankyrin B promotes developmental spine regulation in the mouse prefrontal cortex
Kelsey E Murphy1, Bryce Duncan1, Justin E Sperringer1
1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine at Chapel Hill, Campus Box 7260, Chapel Hill, NC, 27599, United States.
Cerebral Cortex (New York, N.Y. : 1991)
|August 29, 2023
Summary
Ankyrin B regulates dendritic spine density in the developing brain, impacting autism spectrum disorder. Its deletion in mice altered spine formation, revealing a novel role in neural development.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Postnatal development of cortical pyramidal neurons is crucial for brain function.
- Dendritic spine formation and refinement are key processes regulated by molecular interactions.
- Autism spectrum disorder (ASD) is linked to genetic factors affecting neural development, including Ankyrin2.
Purpose of the Study:
- To investigate the role of Ankyrin B in regulating dendritic spine density in the postnatal mouse brain.
- To explore the molecular mechanisms underlying Ankyrin B-mediated spine pruning.
- To understand the implications of Ankyrin B function in the context of autism spectrum disorder.
Main Methods:
- Generated an inducible mouse model (Nex1Cre-ERT2: Ank2flox: RCE) for Ankyrin2 deletion in pyramidal neurons.
- Assessed dendritic spine density in prefrontal cortex layer 2/3 neurons.
- Utilized primary cortical neuron cultures from Ankyrin B-null mice and performed rescue experiments.
- Investigated Ankyrin B binding to neuron-glia related cell adhesion molecule (CAM) using mutant analysis.
Main Results:
- Ankyrin2 deletion in early postnatal development increased spine density in Ankyrin2-deficient mice.
- Ankyrin2 deletion in adulthood did not affect spine density.
- Sema3F-induced spine pruning was impaired in Ankyrin B-null neurons and rescued by the 220 kDa Ankyrin B isoform.
- Ankyrin B binding to neuron-glia related CAM via the FIGQY motif is essential for Sema3F-induced spine pruning.
Conclusions:
- Ankyrin B plays a critical role in postnatal regulation of dendritic spine density.
- Specific Ankyrin B isoforms and binding interactions are vital for activity-dependent spine refinement.
- This research identifies a novel molecular pathway in neural development relevant to autism spectrum disorder.
