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CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

Finney, Brenda A and Schweighoffer, Edina and Navarro-Núñez, Leyre and Bénézech, Cecile and Barone, Francesca and Hughes, Craig E and Langan, Stacey A and Lowe, Kate L and Pollitt, Alice Y and Mourao-Sa, Diego and Sheardown, Steve and Nash, Gerard B and Smithers, Nicholas and Reis e Sousa, Caetano and Tybulewicz, Victor L J and Watson, Steve P (2011) CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development. Blood. ISSN 0006-4971 (Submitted)

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The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro.

Type of Work:Article
Date:2011 (Submission)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Centre for Cardiovascular Sciences
Subjects:R Medicine (General)
Institution:University of Birmingham
Copyright Holders:American Society of Hematology
ID Code:1011
Refereed:YES
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