Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/101549
Title: Divergence of zebrafish and mouse lymphatic cell fate specification pathways
Authors: Impel, Andreas van
Zhao, Zhonghua
Hermkens, Dorien M. A.
Roukens, M. Guy
Fischer, Johanna C.
Peterson-Maduro, Josi
Duckers, Henricus
Ober, Elke A.
Ingham, Philip William
Schulte-Merker, Stefan
Keywords: DRNTU::Science::Biological sciences::Zoology::Anatomy
Issue Date: 2014
Source: Impel, A. v., Zhao, Z., Hermkens, D. M. A., Roukens, M. G., Fischer, J. C., Peterson-Maduro, J., et al. (2014). Divergence of zebrafish and mouse lymphatic cell fate specification pathways. Development, 141(6), 1228-1238.
Series/Report no.: Development
Abstract: In mammals, the homeodomain transcription factor Prox1 acts as the central regulator of lymphatic cell fate. Its restricted expression in a subset of cardinal vein cells leads to a switch towards lymphatic specification and hence represents a prerequisite for the initiation of lymphangiogenesis. Murine Prox1-null embryos lack lymphatic structures, and sustained expression of Prox1 is indispensable for the maintenance of lymphatic cell fate even at adult stages, highlighting the unique importance of this gene for the lymphatic lineage. Whether this pre-eminent role of Prox1 within the lymphatic vasculature is conserved in other vertebrate classes has remained unresolved, mainly owing to the lack of availability of loss-of-function mutants. Here, we re-examine the role of Prox1a in zebrafish lymphangiogenesis. First, using a transgenic reporter line, we show that prox1a is initially expressed in different endothelial compartments, becoming restricted to lymphatic endothelial cells only at later stages. Second, using targeted mutagenesis, we show that Prox1a is dispensable for lymphatic specification and subsequent lymphangiogenesis in zebrafish. In line with this result, we found that the functionally related transcription factors Coup-TFII and Sox18 are also dispensable for lymphangiogenesis. Together, these findings suggest that lymphatic commitment in zebrafish and mice is controlled in fundamentally different ways.
URI: https://hdl.handle.net/10356/101549
http://hdl.handle.net/10220/24154
DOI: http://dx.doi.org/10.1242/dev.105031
Rights: © 2014 The Authors(published by The Company of Biologists Ltd.) This is the author created version of a work that has been peer reviewed and accepted for publication in Development, published by The Company of Biologists Ltd. on behalf of The Authors. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document.  The published version is available at: [Article DOI: http://dx.doi.org/10.1242/dev.105031].
metadata.item.grantfulltext: open
metadata.item.fulltext: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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