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

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.

Pubmed ID: 22186994

Authors

  • Finney BA
  • Schweighoffer E
  • Navarro-Núñez L
  • Bénézech C
  • Barone F
  • Hughes CE
  • Langan SA
  • Lowe KL
  • Pollitt AY
  • Mourao-Sa D
  • Sheardown S
  • Nash GB
  • Smithers N
  • Reis e Sousa C
  • Tybulewicz VL
  • Watson SP

Journal

Blood

Publication Data

February 16, 2012

Associated Grants

  • Agency: Wellcome Trust, Id: 088410
  • Agency: British Heart Foundation, Id: CH/03/003
  • Agency: Medical Research Council, Id: MC_U117527252
  • Agency: British Heart Foundation, Id: PG/11/119/29299

Mesh Terms

  • Animals
  • Animals, Newborn
  • Blood Platelets
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Growth and Development
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Megakaryocytes
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pregnancy
  • Protein-Tyrosine Kinases
  • Thrombopoiesis