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Role of synectin in lymphatic development in zebrafish and frogs

Hermans, K. and Claes, F. and Vandevelde, W. and Zheng, W. and Geudens, I. and Orsenigo, F. and Smet De, F. and Gjini, E. and Anthonis, K. and Ren, B. and Kerjaschki, D. and Autiero, M. and Ny, A. and Simons, M. and Dewerchin, M. and Schulte-Merker, S. and Dejana, E. and Alitalo, K. and Carmeliet, P. (2010) Role of synectin in lymphatic development in zebrafish and frogs. Blood, 116, 3356-66. ISSN 0006-4971.

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Official URL: http://dx.doi.org/10.1182/blood-2009-11-254557

Abstract

The molecular basis of lymphangiogenesis remains incompletely characterized. Here, we document a novel role for the PDZ domain-containing scaffold protein synectin in lymphangiogenesis using genetic studies in zebrafish and tadpoles. In zebrafish, the thoracic duct arises from parachordal lymphangioblast cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein. Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct, due to selective defects in lymphangiogenic but not angiogenic sprouting. Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis. Silencing of synectin in tadpoles caused lymphatic defects due to an underdevelopment and impaired migration of Prox-1(+) lymphatic endothelial cells. Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and vascular endothelial growth factor C-induced migration of lymphatic endothelial cells in vitro. These findings reveal a novel role for synectin in lymphatic development.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9520
Deposited On:07 Feb 2011 01:00
Last Modified:07 Sep 2011 17:01

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