title: Expression of lymphatic markers during avian and mouse cardiogenesis.
abstract: The adult heart has been reported to have an extensive lymphatic system, yet the development of this important system during cardiogenesis is still largely unexplored. The nuclear-localized transcription factor Prox-1 identified a sheet of Prox-1-positive cells on the developing aorta and pulmonary trunk in avian and murine embryos just before septation of the four heart chambers. The cells coalesced into a branching lymphatic network that spread within the epicardium to cover the heart. These vessels eventually expressed the lymphatic markers LYVE-1, VEGFR-3, and podoplanin. Before the Prox-1-positive cells were detected in the mouse epicardium, LYVE-1, a homologue of the CD44 glycoprotein, was primarily expressed in individual epicardial cells. Similar staining patterns were observed for CD44 in avian embryos. The proximity of these LYVE-1/CD44-positive mesenchymal cells to Prox-1-positive vessels suggests that they may become incorporated into the lymphatics. Unexpectedly, we detected LYVE-1/PECAM/VEGFR-3-positive vessels within the embryonic and adult myocardium, which remained Prox-1/podoplanin-negative. Lymphatic markers were surprisingly found in adult rat and embryonic mouse epicardial cell lines, with Prox-1 also exhibiting nuclear-localized expression in primary cultures of embryonic avian epicardial cells. Our data identified three types of cells in the embryonic heart expressing lymphatic markers: (1) Prox-1-positive cells from an extracardiac source that migrate within the serosa of the outflow tract into the epicardium of the developing heart, (2) individual LYVE-1-positive cells in the epicardium that may be incorporated into the Prox-1-positive lymphatic vasculature, and (3) LYVE-1-positive cells/vessels in the myocardium that do not become Prox-1-positive even in the adult heart.
authors: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Ganga
authors: G
authors: Karunamuni
authors: Ke
authors: K
authors: Yang
authors: Yong Qiu
authors: YQ
authors: Doughman
authors: Jamie
authors: J
authors: Wikenheiser
authors: David
authors: D
authors: Bader
authors: Joey
authors: J
authors: Barnett
authors: Anita
authors: A
authors: Austin
authors: Patricia
authors: P
authors: Parsons-Wingerter
authors: Michiko
authors: M
authors: Watanabe
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D005865:Gestational Age; D006023:Glycoproteins / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism; D018960:Hyaluronan Receptors; D007150:Immunohistochemistry; D008208:Lymphatic System / Q000196:embryology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D009024:Morphogenesis; D009206:Myocardium / Q000378:metabolism*; D010496:Pericardium / Q000196:embryology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011784:Quail; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
chemical_list: D030161:Avian Proteins; D015415:Biomarkers; D006023:Glycoproteins; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3; D000098551:Prospero-Related Homeobox 1 Protein; C476399:Cd44 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C492273:LYVE1 protein, mouse