Expression of lymphatic markers during avian and mouse cardiogenesis.
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.
Karunamuni
Ganga
G
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA.
Yang
Ke
K
Doughman
Yong Qiu
YQ
Wikenheiser
Jamie
J
Bader
David
D
Barnett
Joey
J
Austin
Anita
A
Parsons-Wingerter
Patricia
P
Watanabe
Michiko
M
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
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