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Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis

Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis
Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis
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.

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

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.
megakaryocytes, platelets, lymphatics, Meisl, angiogenesis, lymphangiogenesis
0009-7330
1197-1201
Carramolino, Laura
18f3f71e-1e9e-4b4d-b846-ec4507f7b1fc
Fuentes, Joana
7f7d51c6-4b90-49d1-a7df-07baccfb8fbf
García-Andrés, Clara
b403b172-4628-486c-bf83-a173f4d544b6
Azcoitia, Valeria
3e4420a8-c1e5-409f-8752-e18a930c7dbc
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Torres, Miguel
f025b84b-7185-4d05-8b6e-d1823849c9e6
Carramolino, Laura
18f3f71e-1e9e-4b4d-b846-ec4507f7b1fc
Fuentes, Joana
7f7d51c6-4b90-49d1-a7df-07baccfb8fbf
García-Andrés, Clara
b403b172-4628-486c-bf83-a173f4d544b6
Azcoitia, Valeria
3e4420a8-c1e5-409f-8752-e18a930c7dbc
Riethmacher, Dieter
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Torres, Miguel
f025b84b-7185-4d05-8b6e-d1823849c9e6

Carramolino, Laura, Fuentes, Joana, García-Andrés, Clara, Azcoitia, Valeria, Riethmacher, Dieter and Torres, Miguel (2010) Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. Circulation Research, 106 (7), 1197-1201. (doi:10.1161/CIRCRESAHA.110.218073).

Record type: Article

Abstract

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.

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

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.

Full text not available from this repository.

More information

Submitted date: 29 January 2010
Published date: 22 February 2010
Keywords: megakaryocytes, platelets, lymphatics, Meisl, angiogenesis, lymphangiogenesis

Identifiers

Local EPrints ID: 73459
URI: https://eprints.soton.ac.uk/id/eprint/73459
ISSN: 0009-7330
PURE UUID: 68829835-9458-4c13-a67b-a4140e27b4d1

Catalogue record

Date deposited: 08 Mar 2010
Last modified: 18 Jul 2017 23:50

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Contributors

Author: Laura Carramolino
Author: Joana Fuentes
Author: Clara García-Andrés
Author: Valeria Azcoitia
Author: Miguel Torres

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