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Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development
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Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development
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Dissertation
Cellular and Molecular Mechanisms of Blood-Brain and Blood-Spinal Cord Barrier Heterogeneity During Development
2025
Overview
The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) regulate exchange between the peripheral circulation and the central nervous system (CNS). During development, these barriers have a selective permeability that differs from adult states, creating both vulnerabilities and therapeutic opportunities. This dissertation addresses fundamental questions about blood-CNS barrier during development. (1) What endothelial and mural cell subtypes are present during early CNS vascular development? (2) How do these subtypes map to regions of differing barrier permeability? (3) What molecular signatures distinguish these regions? Chapter 2 presents a single-cell atlas of mouse brain and spinal cord vasculature at embryonic day (E)13.5 and E18.5, identifying endothelial and mural subtypes that establish arteriovenous zonation. Trajectory analysis revealed maturation programs progressing from proliferation through angiogenesis to transporter-rich barrier states, with region-specific signatures distinguishing brain from spinal cord. Chapter 3 developed a \"BBB scorecard\" quantifying CNS-specific signatures. Combined with permeability mapping and RNA in situ hybridization, permeable zones align with specific vascular subtypes. Col15a1 was identified as a potential marker of permeable territories. Chapter 4 investigated immune-vascular interactions, identifying galectin-9 as a potential mediator and CD206+ macrophages in multiple positions relative to vessels, consistent with transmigration. These findings establish underscore vascular subtype composition and regional specialization in blood-CNS barrier function.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798270226480
