Divergence of zebrafish and mouse lymphatic cell fate specification pathways
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Divergence of zebrafish and mouse lymphatic cell fate specification pathways. / van Impel, Andreas; Zhao, Zhonghua; Hermkens, Dorien M A; Roukens, M Guy; Fischer, Johanna C; Peterson-Maduro, Josi; Duckers, Henricus; Ober, Elke; Ingham, Philip W; Schulte-Merker, Stefan.
In: Development, Vol. 141, No. 6, 03.2014, p. 1228-38.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Divergence of zebrafish and mouse lymphatic cell fate specification pathways
AU - van Impel, Andreas
AU - Zhao, Zhonghua
AU - Hermkens, Dorien M A
AU - Roukens, M Guy
AU - Fischer, Johanna C
AU - Peterson-Maduro, Josi
AU - Duckers, Henricus
AU - Ober, Elke
AU - Ingham, Philip W
AU - Schulte-Merker, Stefan
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Genetically Modified
KW - COUP Transcription Factor II
KW - Cell Differentiation
KW - Cell Lineage
KW - Endothelial Cells
KW - Gene Expression Regulation, Developmental
KW - Homeodomain Proteins
KW - Lymphangiogenesis
KW - Lymphatic Vessels
KW - Mice
KW - Mice, Knockout
KW - Mutation
KW - SOXF Transcription Factors
KW - Species Specificity
KW - Tumor Suppressor Proteins
KW - Zebrafish
KW - Zebrafish Proteins
U2 - 10.1242/dev.105031
DO - 10.1242/dev.105031
M3 - Journal article
C2 - 24523456
VL - 141
SP - 1228
EP - 1238
JO - Development
JF - Development
SN - 0950-1991
IS - 6
ER -
ID: 128522738