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

Finney, B. A., Schweighoffer, E., Navarro-Núñez, L., Bénézech, C., Barone, F., Hughes, C. E. ORCID: https://orcid.org/0000-0002-9790-5820, Langan, S. A., Lowe, K. L., Pollitt, A. Y. ORCID: https://orcid.org/0000-0001-8706-5154, Mourao-Sa, D., Sheardown, S., Nash, G. B., Smithers, N., Reis e Sousa, C., Tybulewicz, V. L. J. and Watson, S. P. (2012) CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development. Blood, 119 (7). pp. 1747-1756. ISSN 0006-4971 doi: 10.1182/blood-2011-09-380709

Abstract/Summary

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 hematopoietic 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 hematopoietic 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 depends on CLEC-2 and Syk. These studies found 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 behavior in vitro.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/44573
Identification Number/DOI	10.1182/blood-2011-09-380709
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	American Society of Hematology
Download/View statistics	View download statistics for this item