Embryonic development and malformation of lymphatic vessels.
In the human, malformations of lymphatic vessels can be observed as lymphangiectasia, lymphangioma and lymphangiomatosis, with a prevalence of 1.2-2.8 per thousand. Their aetiology is unknown and a causal therapy does not exist. We investigated the origin of lymphatic endothelial cells (LECs) in avian and murine embryos, and compared the molecular profile of LECs from normal and malformed lymphatics of children. In avian embryos, Prox1+ lymphangioblasts are located in the confluence of the cranial and caudal cardinal veins, where the jugular lymph sac (JLS) forms. Cell lineage studies show that the JLS is of venous origin. In contrast, the lymphatics of the dermis are derived from mesenchymal lymphangioblasts located in the dermatomes, suggesting a dual origin of LECs in avian embryos. The same may hold true for murine embryos, where Lyve1+ LEC precursors are found in the cardinal veins, and in the mesenchyme. The mesenchymal cells express the pan-leukocyte marker CD45, indicating a cell type with lymphendothelial and leukocyte characteristics. In the human, such cells might give rise to Kaposi's sarcoma. Microarray analyses of LECs from lymphangiomas of children show a large number of regulated genes, such as VEGFR3. Our studies show that lymphvasculogenesis and lymphangiogenesis occur simultaneously in the embryo, and suggest a function for VEGFR3 in lymphangiomas.
Wilting
Jörg
J
Department of Pediatrics 1, Georg-August-University, Goettingen, Germany.
Buttler
Kerstin
K
Rössler
Jochen
J
Norgall
Susanne
S
Schweigerer
Lothar
L
Weich
Herbert A
HA
Papoutsi
Maria
M
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002648:Child; D004625:Embryo, Nonmammalian / Q000166:cytology; D047108:Embryonic Development; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D042601:Lymphatic Vessels / Q000002:abnormalities* / Q000196:embryology*; D051379:Mice; D011784:Quail; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D040321:Vascular Endothelial Growth Factor Receptor-3