Prox1, master regulator of the lymphatic vasculature phenotype.
In contrast to the extensive molecular and functional characterization of blood vascular endothelium, little is known about the mechanisms that control the formation and lineage-specific differentiation and function of lymphatic vessels. The homeobox gene Prox1, the vertebrate homologue of the Drosophila prospero gene, has been recently identified to be required for the induction of lymphatic vascular development from preexisting embryonic veins, and studies in Prox1-deficient mice have confirmed Florence Sabin's original hypothesis about the origin of the lymphatic vascular system from embryonic veins. The recent establishment of cell culture models for the selective propagation of blood vascular and lymphatic endothelial cells, together with the findings that these cells maintain their lineage-specific differentiation in vitro, has led to the discovery that Prox1 expression is sufficient to induce a lymphatic phenotype in blood vascular endothelium. Ectopic expression of Prox1 downregulated blood vascular-associated genes and also upregulated some of the known lymphatic endothelial cell markers. Together, these studies suggest that the blood vascular phenotype represents the default endothelial differentiation and they identify an essential role of Prox1 in the program specifying lymphatic endothelial cell fate.
Hong
Young-Kwon
YK
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Massachusetts, Boston, USA. young.hong@cbrc2.mgh.harvard.edu
Detmar
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004627:Embryonic Induction; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000196:embryology; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008208:Lymphatic System / Q000166:cytology* / Q000196:embryology*; D008969:Molecular Sequence Data; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein