Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis.
BACKGROUND
Several mutations that impair the development of blood lineages in the mouse also impair the formation of the lymphatic vasculature and its separation from the blood vasculature. However, the basis for these defects has remained unknown because the mutations characterized affect more than one blood lineage.


OBJECTIVE
We tested the hypothesis that megakaryocytes/platelets are required for the formation of the lymphatic vasculature and its separation from the blood vascular system.


RESULTS
We characterized the vascular patterning defects of mice deficient for the homeodomain transcription factor Meis1 (myeloid ecotropic viral integration site 1), which completely lack megakaryocyte/platelets. Meis1 null embryos fail to separate the blood and lymphatic vasculature, showing blood-filled primary lymphatic sacs and superficial lymphatic vessels. To test the involvement of megakaryocytes/platelets in this phenotype, we generated megakaryocyte/platelet-specific deficient mice by targeted lineage ablation, without affecting other blood lineages. This model reproduces the lymphatic/blood vasculature separation defects observed in Meis1 mutants. A similar phenotype was induced by antibody-mediated ablation of circulating platelets in wild type mice. Strong association of platelets with vascular endothelium at regions of contact between lymphatic sacs and veins confirmed a direct role of platelets in the separation of the 2 vasculatures.


CONCLUSIONS
In addition to their known protective function in the response accidental vascular injury, platelets are also required during embryonic lymphangiogenesis for the separation of the nascent lymphatic vasculature from blood vessels.
Carramolino
Laura
L
Departamento de Biología del Desarrollo Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain.
Fuentes
Joana
J
García-Andrés
Clara
C
Azcoitia
Valeria
V
Riethmacher
Dieter
D
Torres
Miguel
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D019070:Cell Lineage; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D042583:Lymphangiogenesis / Q000235:genetics; D042601:Lymphatic Vessels / Q000196:embryology* / Q000378:metabolism; D008533:Megakaryocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy
D000906:Antibodies; D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins