A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development
Pichol-Thievend, Cathy; Betterman, Kelly L.; Liu, Xiaolei; Ma, Wanshu; Skoczylas, Renae; Lesieur, Emmanuelle; Bos, Frank L.; Schulte, Dorte; Schulte-Merker, Stefan; Hogan, Benjamin M.; Oliver, Guillermo; Harvey, Natasha L.; Francois, Mathias
(2018) Development (Cambridge), volume 145, issue 10
(Article)
Abstract
Despite the essential role of the lymphatic vasculature in tissue homeostasis and disease, knowledge of the organ-specific origins of lymphatic endothelial progenitor cells remains limited. The assumption that most murine embryonic lymphatic endothelial cells (LECs) are venous derived has recently been challenged. Here, we show that the embryonic dermal blood
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capillary plexus constitutes an additional, local source of LECs that contributes to the formation of the dermal lymphatic vascular network. We describe a novel mechanism whereby rare PROX1-positive endothelial cells exit the capillary plexus in a Ccbe1-dependent manner to establish discrete LEC clusters. As development proceeds, these clusters expand and further contribute to the growing lymphatic system. Lineage tracing and analyses of Gata2-deficient mice confirmed that these clusters are endothelial in origin. Furthermore, ectopic expression of Vegfc in the vasculature increased the number of PROX1-positive progenitors within the capillary bed. Our work reveals a novel source of lymphatic endothelial progenitors employed during construction of the dermal lymphatic vasculature and demonstrates that the blood vasculature is likely to remain an ongoing source of LECs during organogenesis, raising the question of whether a similar mechanism operates during pathological lymphangiogenesis.
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Keywords: Lineage tracing, Lymphangiogenesis, Lymphatic endothelial cells, Mouse genetics, Progenitor cell, PROX1, Skin, Molecular Biology, Developmental Biology
ISSN: 0950-1991
Publisher: Company of Biologists Ltd
Note: Funding Information: We thank Chris Brown and staff at the SA Pathology Animal Facility for animal husbandry. Transgenic (Tie2-GFP) embryonic material was provided by Frank Bos and Jacco van Rheenen (Hubrecht Institute). Imaging at IMB was supported by ACRF microscopy facility. The DSHB Hybridoma Product 8.1.1 (podoplanin) developed by A. G. Farr (University of Washington) was obtained from the Developmental Studies Hybridoma Bank, created by The NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA, 52242, USA. This work was supported by grants from the National Health and Medical Research Council (NHMRC) (APP1107643 to M.F. and N.L.H.), Australian Research Council (ARC) (DP150103110 to B.M.H. and N.L.H.) and National Institutes of Health (R01-HL073402 to G.O.). N.L.H. is supported by an ARC Future Fellowship (FT130101254). M.F. is supported by an NHMRC Career Developmental Fellowship (APP1111169). B.M.H. is supported by an NHMRC/National Heart Foundation of Australia Career Development Fellowship (1083811). F.L.B. was supported by Netherlands Cancer Society (KWF Kankerbestrijding) Fellowship 6660. Deposited in PMC for release after 12 months. Funding Information: This work was supported by grants from the National Health and Medical Research Council (NHMRC) (APP1107643 to M.F. and N.L.H.), Australian Research Council (ARC) (DP150103110 to B.M.H. and N.L.H.) and National Institutes of Health (R01-HL073402 to G.O.). N.L.H. is supported by an ARC Future Fellowship (FT130101254). M.F. is supported by an NHMRC Career Developmental Fellowship (APP1111169). B.M.H. is supported by an NHMRC/National Heart Foundation of Australia Career Development Fellowship (1083811). F.L.B. was supported by Netherlands Cancer Society (KWF Kankerbestrijding) Fellowship 6660. Deposited in PMC for release after 12 months. Publisher Copyright: © 2018. Published by The Company of Biologists Ltd.
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