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.
