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Published on: January 14, 2020
"PDGFRα is required for postnatal cerebral perivascular fibroblast development"
Hannah E Jones1,2, Kelsey A Abrams1,2, Katherine A Fantauzzo2,3
1Department of Pediatrics, Section of Developmental Biology, Anschutz Medical Campus Aurora, CO, USA 80025.
Insights
Platelet-derived growth factor receptor alpha (PDGFRα) signaling is crucial for the development of perivascular fibroblasts (PVFs) in the brain. Impaired PDGFRα signaling disrupts PVF and perivascular macrophage coverage of cerebral vessels.
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 has been studied, the underlying molecular mechanisms remain largely unknown.
- PVFs express platelet-derived growth factor receptors (PDGFRs), suggesting a role for PDGF signaling.
Purpose of the Study:
- To investigate the role of PDGF signaling in the developmental mechanisms of PVFs.
- To determine the specific contribution of PDGFRα to PVF development and vascular coverage.
Main Methods:
- Immunohistochemistry and RNA transcript detection were used to analyze PDGFR expression in PVFs and PDGF ligand distribution.
- Conditional deletion of PDGFRα in fibroblasts was performed using the Col1a2-CreERT mouse line.
Main Results:
- Developmental expression of PDGFRs by PVFs and PDGF ligand distribution in the brain were characterized.
- Postnatal deletion of PDGFRα significantly impaired PVF coverage of cerebral vessels at postnatal day 10.
- Perivascular macrophage coverage of cerebral vessels was also impaired in PDGFRα conditional mutants.
Conclusions:
- PDGFRα signaling is essential for proper PVF development and vascular coverage in the postnatal brain.
- These findings highlight PDGFRα as a critical regulator of PVF development and may inform studies on PVFs in 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 significantly 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.
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