TY - JOUR
T1 - CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development.
AU - Finney, Brenda A
AU - Schweighoffer, Edina
AU - Navarro-Núñez, Leyre
AU - Benezech, Cecile
AU - Barone, Francesco
AU - Hughes, Craig E
AU - Langan, Stacey A
AU - Lowe, Kate L
AU - Pollitt, Alice Y
AU - Mourao-Sa, Diego
AU - Sheardown, Steven
AU - Nash, Gerard B
AU - Smithers, Nicholas
AU - Reis e Sousa, Caetano
AU - Tybulewicz, Victor L J
AU - Watson, Steve P
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
U2 - 10.1182%2Fblood-2011-09-380709
DO - 10.1182%2Fblood-2011-09-380709
M3 - Article
SN - 0006-4971
VL - 119
SP - 1747
EP - 1756
JO - Blood
JF - Blood
IS - 7
ER -