Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions

Area of Science:

• Neuroscience
• Developmental Biology
• Vascular Biology

Background:

• Neurovascular unit (NVU) interactions are vital for brain development, but regional differences and developmental regulation remain unclear.
• Understanding NVU communication is key to deciphering brain region-specific vascular patterning and homeostasis.

Purpose of the Study:

• To map cortical and thalamic NVU communication dynamics during postnatal development.
• To investigate how region-specific NVU interactions regulate vascular patterning and maturation.

Main Methods:

• Spatial transcriptomics and region-resolved single-cell RNA sequencing in postnatal mouse brains.
• Analysis of endothelial cell programs and neuronal-glial maturation.
• Investigating the role of TGFβ2 signaling in thalamic vascularization.

Main Results:

• Spatiotemporal divergence in endothelial cell programs between cortical and thalamic regions.
• Neuronal and glial maturation correlates with region-specific angiogenic trajectories.
• Neuronal-endothelial TGFβ2 signaling is essential for thalamic vascularization.
• Loss of endothelial TGFβR1 signaling causes mTOR hyperactivation, leading to thalamus-predominant vascular malformations and hemorrhage.

Conclusions:

• Postnatal angiogenesis and vascular maturation are coordinated by circuit maturation and region-specific NVU communication.
• TGFβ2 signaling and mTOR pathway are critical regulators of thalamic vascular development.
• Findings provide a framework for understanding regional vulnerability in neurovascular disorders.