Abstract

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. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, U19NS123719, NS102237, F31NS134252 National Institute of General Medical Sciences, https://ror.org/04q48ey07, T32GM007171-47, T32GM145449-01 American Heart Association, https://ror.org/013kjyp64, 25PRE1357000