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Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis
Siyuan Cheng1,2,3, Ivan Fan Xia1,2,3, Renate Wanner1,2,3
1Department of Genetics, Yale School of Medicine, 333 Cedar St, New Haven, CT 06520, USA.
Biorxiv : the Preprint Server for Biology
|December 11, 2023
Summary
Vascular smooth muscle cell differentiation in brain arteries is regulated by blood flow. Endothelial klf2a activation by blood flow is key for this crucial process in cerebrovascular development.
Area of Science:
- Neuroscience
- Developmental Biology
- Vascular Biology
Background:
- Vascular smooth muscle cells (VSMCs) are vital for regulating cerebral blood flow and neurovascular coupling.
- VSMC dedifferentiation is linked to cerebrovascular diseases and neurodegeneration.
- The developmental process of VSMC differentiation on brain arteries is not well understood.
Approach:
- Investigated VSMC differentiation on the zebrafish circle of Willis (CoW).
- Observed endothelial cell migration and subsequent VSMC differentiation from progenitor cells.
- Analyzed the role of blood flow and the transcription factor klf2a.
Key Points:
- VSMC differentiation on CoW arteries follows a spatiotemporal pattern, from anterior to posterior.
- Earlier VSMC differentiation in anterior CoW arteries correlates with higher wall shear stress.
- Pulsatile blood flow is essential for VSMC differentiation in both zebrafish and human brain models.
- Endothelial klf2a activation precedes VSMC differentiation and is required for the process.
Conclusions:
- Blood flow-activated endothelial klf2a is a critical mechanism regulating initial VSMC differentiation on vertebrate brain arteries.
- Understanding VSMC differentiation is crucial for developing strategies for cerebrovascular diseases.
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