δ-catenin controls layer-specific transcriptional maturation of astrocytes via Zbtb20
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Coordinated maturation of diverse neural cell types drives mammalian cortical circuit development. Disruption of this coordination is a hallmark of human neurodevelopmental disorders, yet mechanisms that synchronize transcriptional maturation across cell types remain poorly understood. Here, we identify δ-catenin ( Ctnnd2 ), a component of adherens junctions, that links cell–cell interactions to transcriptional regulation. Using single-nucleus and spatial transcriptomics, we show that δ-catenin loss disrupts transcriptional maturation across neural cell types, particularly in astrocytes. δ-catenin loss impairs acquisition of layer-specific astrocyte identities and prolongs ocular dominance plasticity, indicating impaired circuit stabilization. Mechanistically, we identify the BTB/POZ transcription factor Zbtb20, which is enriched in glial cells, as a key regulator of this process. δ-catenin loss increases Zbtb20 expression, redistributes its genome-wide binding, and dysregulates its target genes. Together, these findings support a model in which δ-catenin regulates Zbtb20-dependent transcriptional programs to establish layer-specific astrocyte identities in coordination with developing cortical circuits.
SUMMARY
Sejourne et al report that loss of the adherens junction protein δ-catenin prolongs ocular dominance plasticity and disrupts astrocyte and oligodendrocyte transcriptional identity. The underlying mechanism seems to rely on the glia-enriched transcription factor Zbtb20, which is upregulated and redistributed upon δ-catenin loss, resulting in altered expression of its target genes.
