Lymphangiogenesis by blind-ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting†
Article first published online: 17 FEB 2006
Published 2006 Wiley-Liss, Inc.
The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume 288A, Issue 3, pages 233–247, March 2006
How to Cite
Parsons-Wingerter, P., Mckay, T. L., Leontiev, D., Vickerman, M. B., Condrich, T. K. and Dicorleto, P. E. (2006), Lymphangiogenesis by blind-ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting. Anat. Rec., 288A: 233–247. doi: 10.1002/ar.a.20309
This article is a US Government work and, as such, is in the public domain in the United States of America.
- Issue published online: 20 FEB 2006
- Article first published online: 17 FEB 2006
- Manuscript Accepted: 5 DEC 2005
- Manuscript Received: 22 NOV 2005
- Internal Research and Development Award. Grant Number: IRD04-54
- Microgravity Science
- John Glenn Research Center
- National Aeronautics and Space Administration
- vascular endothelial growth factor;
- Euclidean distance map;
- chorioallantoic membrane;
Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed “hemangiogenesis”) and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6–E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (αSMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, αSMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF165) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF165 in lymphangiogenesis is less clear. Interestingly, VEGF165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks. Published 2006 Wiley-Liss, Inc.