Ankyrin B Promotes Developmental Spine Regulation in the Mouse Prefrontal Cortex

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Postnatal regulation of dendritic spine formation and refinement in cortical pyramidal neurons is critical for excitatory/inhibitory balance in neocortical networks.
• Class 3 Semaphorins and L1-CAMs mediate selective spine pruning in the mouse prefrontal cortex (PFC).
• Ankyrin B (AnkB), encoded by ANK2, a high-confidence autism spectrum disorder (ASD) gene, binds L1-CAMs.

Approach:

• An inducible mouse model (Nex1Cre-ERT2: Ank2flox: RCE) was used to delete Ank2 in early postnatal pyramidal neurons.
• AnkB’s role in Sema3F-induced spine pruning was assessed in cortical neuron cultures from AnkB-null mice.
• AnkB binding to NrCAM and its effect on spine pruning were investigated using specific mutations.

Key Points:

• Ank2 deletion in early postnatal neurons increased spine density in PFC layer 2/3, while adult deletion had no effect.
• Sema3F-induced spine pruning was impaired in AnkB-null neurons and rescued by the 220 kDa AnkB isoform.
• AnkB binds NrCAM via the cytoplasmic FIGQY motif; mutation to FIGQH disrupted binding and impaired pruning.

Conclusions:

• Ankyrin B (AnkB) plays a novel role in regulating dendritic spine density during postnatal development.
• This AnkB function is essential for Sema3F-mediated spine pruning in the developing cortex.
• Understanding AnkB’s role offers insights into cortical circuit development and potential molecular mechanisms underlying ASD.