The spatiotemporal dynamics of postnatal vascularization in the mouse brain.

Abstract

The structure of the cerebral vasculature is immature at birth and undergoes significant postnatal remodeling and expansion. However, how vascularization progresses throughout the brain to integrate volumetric growth with neuronal circuit maturation is unclear. To address this spatiotemporally, we developed a light-sheet-aligned mouse brain annotated developmental atlas (LAMBADA)-a resource for registering and annotating optically cleared developing mouse brains with high temporal resolution, enriched by aligned spatial transcriptomics. Using this resource, we identified three distinct, brain-wide phases of postnatal cerebral vascular development: (1) an isometric expansion phase characterized by canonical transcriptomic signatures; (2) a regional specialization phase coinciding with neuronal maturation and synaptogenesis; and (3) a refinement phase marked by the stabilization of vascular networks and synapses. We delineated the molecular and structural mechanisms underlying these phases by correlating vascular remodeling with spatial transcriptomic gene expression. This atlas provides a foundation for studying developmental neurovascular interactions and serves as a resource for murine postnatal brain development research.