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Cell Adhesion Mediated by VCAM-ITGα9 Interactions Enables Lymphatic Development.
Yiqing Yang1, David Enis1, Hui Zheng1
1From the Department of Medicine and Cardiovascular Institute (Y.Y., D.E., H.Z., S.C., J.Y., M.C., V.D., M.L.K.) and Department of Dermatology (D.E.), University of Pennsylvania, Philadelphia; and Department of Medicine, University of Washington, Seattle (T.P.).
Vascular cell adhesion molecule (VCAM) and integrin α9 (Itgα9) are crucial for lymphatic development in zebrafish, but not in mice. This highlights species-specific roles in lymphatic vascular growth.
Area of Science:
- Developmental Biology
- Cell Adhesion
- Vascular Biology
Background:
- Cell-cell adhesion molecules, like VCAM, are vital for blood vessel formation.
- Their role in lymphatic vessel development is less understood.
- Integrins are key receptors for VCAM.
Purpose of the Study:
- Investigate the function of VCAM and its receptors, integrins α9 and α4, in lymphatic vascular development.
- Utilize genetic models in zebrafish and mice.
Main Methods:
- Conditional Vcam gene deletion in mice.
- Morpholino knockdown and cRNA rescue of VCAM, integrin α9, and integrin α4 in zebrafish.
- Analysis of lymphatic growth in both species.
Main Results:
- VCAM is essential for lymphatic development in zebrafish embryos.
- Integrin α9, not α4, is the necessary VCAM receptor in developing zebrafish.
- VCAM is present in mouse lymphatic vessels, but its absence only slows growth.
Conclusions:
- Itgα9-VCAM interactions are unexpectedly important for fish lymphatic development, but not mouse.
- Rapid tissue growth, common in early zebrafish development, may amplify the significance of cell adhesion molecules.
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