VEGF and VEGF-C: Specific Induction of Angiogenesis and Lymphangiogenesis in the Differentiated Avian Chorioallantoic Membrane. Oh, S., Jeltsch, M. M., Birkenhäger, R., McCarthy, J. E., Weich, H. A., Christ, B., Alitalo, K., & Wilting, J. Developmental Biology, 188(1):96–109, August, 1997.
VEGF and VEGF-C: Specific Induction of Angiogenesis and Lymphangiogenesis in the Differentiated Avian Chorioallantoic Membrane [link]Paper  doi  abstract   bibtex   1 download  
The lymphangiogenic potency of endothelial growth factors has not been studied to date. This is partially due to the lack ofin vivolymphangiogenesis assays. We have studied the lymphatics of differentiated avian chorioallantoic membrane (CAM) using microinjection of Mercox resin, semi- and ultrathin sectioning, immunohistochemical detection of fibronectin and α-smooth muscle actin, andin situhybridization with VEGFR-2 and VEGFR-3 probes. CAM is drained by lymphatic vessels which are arranged in a regular pattern. Arterioles and arteries are accompanied by a pair of interconnected lymphatics and form a plexus around bigger arteries. Veins are also associated with lymphatics, particularly larger veins, which are surrounded by a lymphatic plexus. The lymphatics are characterized by an extremely thin endothelial lining, pores, and the absence of a basal lamina. Patches of the extracellular matrix can be stained with an antibody against fibronectin. Lymphatic endothelial cells of differentiated CAM show ultrastructural features of this cell type. CAM lymphatics do not possess mediae. In contrast, the lymphatic trunks of the umbilical stalk are invested by a single but discontinuous layer of smooth muscle cells. CAM lymphatics express VEGFR-2 and VEGFR-3. Both the regular pattern and the typical structure of these lymphatics suggest that CAM is a suitable site to study thein vivoeffects of potential lymphangiogenic factors. We have studied the effects of VEGF homo- and heterodimers, VEGF/PlGF heterodimers, and PlGF and VEGF-C homodimers on Day 13 CAM. All the growth factors containing at least one VEGF chain are angiogenic but do not induce lymphangiogenesis. PlGF-1 and PlGF-2 are neither angiogenic nor lymphangiogenic. VEGF-C is the first lymphangiogenic factor and seems to be highly chemoattractive for lymphatic endothelial cells. It induces proliferation of lymphatic endothelial cells and development of new lymphatic sinuses which are directed immediately beneath the chorionic epithelium. Our studies show that VEGF and VEGF-C are specific angiogenic and lymphangiogenic growth factors, respectively.
@article{oh_vegf_1997,
	title = {{VEGF} and {VEGF}-{C}: {Specific} {Induction} of {Angiogenesis} and {Lymphangiogenesis} in the {Differentiated} {Avian} {Chorioallantoic} {Membrane}},
	volume = {188},
	issn = {0012-1606},
	shorttitle = {{VEGF} and {VEGF}-{C}},
	url = {http://dx.doi.org/10.1006/dbio.1997.8639},
	doi = {10.1006/dbio.1997.8639},
	abstract = {The lymphangiogenic potency of endothelial growth factors has not been studied to date. This is partially due to the lack ofin vivolymphangiogenesis assays. We have studied the lymphatics of differentiated avian chorioallantoic membrane (CAM) using microinjection of Mercox resin, semi- and ultrathin sectioning, immunohistochemical detection of fibronectin and α-smooth muscle actin, andin situhybridization with VEGFR-2 and VEGFR-3 probes. CAM is drained by lymphatic vessels which are arranged in a regular pattern. Arterioles and arteries are accompanied by a pair of interconnected lymphatics and form a plexus around bigger arteries. Veins are also associated with lymphatics, particularly larger veins, which are surrounded by a lymphatic plexus. The lymphatics are characterized by an extremely thin endothelial lining, pores, and the absence of a basal lamina. Patches of the extracellular matrix can be stained with an antibody against fibronectin. Lymphatic endothelial cells of differentiated CAM show ultrastructural features of this cell type. CAM lymphatics do not possess mediae. In contrast, the lymphatic trunks of the umbilical stalk are invested by a single but discontinuous layer of smooth muscle cells. CAM lymphatics express VEGFR-2 and VEGFR-3. Both the regular pattern and the typical structure of these lymphatics suggest that CAM is a suitable site to study thein vivoeffects of potential lymphangiogenic factors. We have studied the effects of VEGF homo- and heterodimers, VEGF/PlGF heterodimers, and PlGF and VEGF-C homodimers on Day 13 CAM. All the growth factors containing at least one VEGF chain are angiogenic but do not induce lymphangiogenesis. PlGF-1 and PlGF-2 are neither angiogenic nor lymphangiogenic. VEGF-C is the first lymphangiogenic factor and seems to be highly chemoattractive for lymphatic endothelial cells. It induces proliferation of lymphatic endothelial cells and development of new lymphatic sinuses which are directed immediately beneath the chorionic epithelium. Our studies show that VEGF and VEGF-C are specific angiogenic and lymphangiogenic growth factors, respectively.},
	number = {1},
	urldate = {2012-09-22},
	journal = {Developmental Biology},
	author = {Oh, Su-Ja and Jeltsch, Markku M. and Birkenhäger, Ralf and McCarthy, John E.G. and Weich, Herbert A. and Christ, Bodo and Alitalo, Kari and Wilting, Jörg},
	month = aug,
	year = {1997},
	keywords = {Actins, Animals, Cell Differentiation, Cell Division, Chick Embryo, Chorion, Coturnix, DNA Probes, Endothelial Growth Factors, Fibronectins, Immunohistochemistry, In Situ Hybridization, Lymphatic System, Lymphokines, Microcirculation, Neovascularization, Physiologic, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface, Receptors, Growth Factor, Receptors, Vascular Endothelial Growth Factor, Recombinant Proteins, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-3, Vascular Endothelial Growth Factors, vascular endothelial growth factor C},
	pages = {96--109},
}

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