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Published on: January 14, 2020
PDGFRα is required for postnatal cerebral perivascular fibroblast development
Hannah E Jones1, Kelsey A Abrams1, Sol Kim1
1Department of Pediatrics, Section of Developmental Biology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA; Cell Biology, Stem Cells and Development Graduate Program, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Insights
Platelet-derived growth factor receptor-alpha (PDGFRα) signaling is crucial for the development of perivascular fibroblasts (PVFs) in the brain. This study reveals PDGFRα
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Perivascular fibroblasts (PVFs) are key cells in brain vasculature, implicated in neurovascular function, injury, and neuroinflammation.
- While PVF development dynamics are known, the underlying molecular mechanisms remain elusive.
- PVFs express platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ, suggesting a role for PDGF signaling.
Purpose of the Study:
- To investigate the role of PDGF signaling in the development of brain perivascular fibroblasts (PVFs).
- To determine the necessity of PDGFRα signaling in PVF development and coverage of cerebral vasculature.
Main Methods:
- Immunohistochemistry and RNA transcript detection were used to analyze PDGFR and PDGF ligand expression during development.
- Conditional deletion of PDGFRα in fibroblasts was performed using the Col1a2-CreERT mouse line.
- PVF and perivascular macrophage coverage of cerebral vessels was assessed at postnatal day 10.
Main Results:
- Developmental expression of PDGFRs by PVFs and PDGF ligands in the brain was confirmed.
- Postnatal deletion of PDGFRα in fibroblasts significantly impaired PVF coverage of cerebral vessels.
- Impaired cerebral vessel coverage was also observed in perivascular macrophages, mirroring PVF defects.
Conclusions:
- PDGFRα signaling is essential for normal perivascular fibroblast development and vascular coverage in the postnatal brain.
- These findings identify a critical molecular pathway in PVF development.
- Understanding PDGFRα's role may illuminate aberrant PVF pathways in neurological injury and disease contexts.
Abstract:
Perivascular fibroblasts (PVFs) are a cell type associated with large diameter blood vessels in the brain and spinal cord parenchyma and leptomeninges. PVFs have previously defined roles in injury and neuroinflammatory diseases and predicted roles in supporting neurovascular function. The temporal dynamics of PVF development in the pre- and postnatal cerebral cortex have recently been described, however the molecular mechanisms that underly PVF development have not been identified. PVFs express both platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Here we investigate the role of PDGF signaling in PVF development. We use immunohistochemistry and RNA transcript detection methods to show developmental expression of PDGFRs by PVFs and examine distribution of PDGF ligand expression in the brain. We show that postnatal deletion of PDGFRα in fibroblasts using the Col1a2-CreERT mouse line impairs PVF coverage of cerebral vessels at postnatal day 10. Perivascular macrophages, a cell type previously shown to co-develop with PVFs, have impaired cerebral vessel coverage in conditional mutants that is similar to PVF coverage defects. This work establishes a requirement for PDGFRα signaling in PVF development and may shed light upon the potential pathways that are over-activated in PVFs in injury and disease contexts.
