A molecular atlas of brain neurovascular interactions reveals a spatiotemporal requirement of TGFβ signaling in brain angiogenesis [Visium]

Neurovascular unit (NVU) communications guide vascular patterning, BBB maturation, and neuronal homeostasis, yet whether these interactions differ across brain regions and how they regulate the vasculature during development remains unclear. Here, we combine spatial transcriptomics with region-resolved endothelial single-cell RNA sequencing in the postnatal mouse brain to map cortical and thalamic NVU communication dynamics. We uncover spatiotemporal divergence of endothelial programs and show that neuronal and glial maturation parallels region-specific angiogenic trajectories. We identify neuronal–endothelial TGFβ2 signaling as an essential regulator of thalamic vascularization during a defined postnatal developmental window. Loss of endothelial TGFβR1 signaling leads to mTOR hyperactivation and thalamus-predominant vascular malformations and hemorrhage within this developmental window, and these defects are rescued by mTOR inhibition. Together, these findings show that circuit maturation and region-specific NVU communication programs coordinate postnatal angiogenesis and vascular maturation, providing a framework for understanding regional vulnerability in neurovascular disorders.