title: Divergence of zebrafish and mouse lymphatic cell fate specification pathways.
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.
authors: Hubrecht Institute - KNAW & UMC Utrecht, 3584 CT Utrecht, The Netherlands.
authors: Andreas
authors: A
authors: van Impel
authors: Zhonghua
authors: Z
authors: Zhao
authors: Dorien M A
authors: DM
authors: Hermkens
authors: M Guy
authors: MG
authors: Roukens
authors: Johanna C
authors: JC
authors: Fischer
authors: Josi
authors: J
authors: Peterson-Maduro
authors: Henricus
authors: H
authors: Duckers
authors: Elke A
authors: EA
authors: Ober
authors: Philip W
authors: PW
authors: Ingham
authors: Stefan
authors: S
authors: Schulte-Merker
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051837:COUP Transcription Factor II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D042601:Lymphatic Vessels / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D055760:SOXF Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D051837:COUP Transcription Factor II; D018398:Homeodomain Proteins; D055760:SOXF Transcription Factors; C526282:Sox18 protein, zebrafish; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; D000098551:Prospero-Related Homeobox 1 Protein
keywords: Coup-TFII; Lymphangiogenesis; Nr2f2; Prox1; Sox18