Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

Nature Communications, 2017 · DOI: 10.1038/ncomms13991 · Published: January 10, 2017

Cardiovascular Science Neurology Genetics

Simple Explanation

This study investigates how developing zebrafish spinal cord neurons control blood vessel growth. It focuses on two key proteins: Vegfaa, which promotes blood vessel growth, and sFlt1, which restricts it. The researchers found that neurons balance Vegfaa and sFlt1 to regulate angiogenesis (blood vessel formation) near the spinal cord. The study also discovered a new way blood vessels sprout from veins, influenced by neuronal sFlt1 and Vegfaa. This sprouting mode is different from previously known arterial or venous sprouting.

Study Duration

Not specified

Participants

Zebrafish embryos

Evidence Level

Not specified

Key Findings

1
Neuronal sFlt1 restricts angiogenesis around the spinal cord by limiting Vegfaa availability.
2
Loss of neuronal sFlt1 leads to increased angiogenesis and the formation of a vascular network supplying the spinal cord, dependent on Vegfaa-Kdrl signaling.
3
Spinal cord vascularization proceeds from veins involving regulation of neuronal sFlt1 and Vegfaa.

Research Summary

The study elucidates how developing zebrafish spinal cord neurons coordinate vessel growth by balancing neuron-derived Vegfaa and sFlt1, which restricts angiogenesis at the neurovascular interface. Loss of neuronal sFlt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation, with sprouts invading the neural tube under specific conditions. The data suggest that spinal cord vascularization proceeds from veins, regulated by a two-tiered mechanism involving neuronal sFlt1 and Vegfaa, representing a novel sprouting mode.

Practical Implications

Therapeutic Angiogenesis

Understanding the balance between Vegfaa and sFlt1 could inform strategies for promoting therapeutic angiogenesis in the nervous system after injury or in neurodegenerative diseases.

Anti-angiogenic Therapies

The findings may also provide insights into developing targeted anti-angiogenic therapies for conditions where excessive blood vessel growth in the spinal cord is detrimental.

Understanding Vascular Development

The discovery of a novel venous sprouting mode contributes to a better understanding of the diversity and regulation of vascular development in different tissues and organs.

Study Limitations

1
The study is performed on zebrafish, and findings may not be directly translatable to mammals.
2
The precise molecular mechanisms downstream of Vegfaa and sFlt1 in regulating venous sprouting require further investigation.
3
The role of other cell types and signaling pathways in the spinal cord microenvironment in modulating angiogenesis needs further exploration.

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