VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia
Holger Gerhardt,Matthew Golding,Marcus Fruttiger,Christiana Ruhrberg,Andrea Lundkvist,Alexandra Abramsson,Michael Jeltsch,Christopher A. Mitchell,Kari Alitalo,David T. Shima,Christer Betsholtz +10 more
TLDR
It is shown here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts.Abstract:
Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. It controls several processes in endothelial cells, such as proliferation, survival, and migration, but it is not known how these are coordinately regulated to result in more complex morphogenetic events, such as tubular sprouting, fusion, and network formation. We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts. The tip cells respond to VEGF-A only by guided migration; the proliferative response to VEGF-A occurs in the sprout stalks. These two cellular responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2. Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is regulated by its concentration. Thus, vessel patterning during retinal angiogenesis depends on the balance between two different qualities of the extracellular VEGF-A distribution, which regulate distinct cellular responses in defined populations of endothelial cells.read more
Citations
More filters
Journal ArticleDOI
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
TL;DR: These findings support developments of new therapeutic approaches for chronic neurodegenerative disorders directed at the blood-brain barrier and other nonneuronal cells of the neurovascular unit.
Journal ArticleDOI
Collective cell migration in morphogenesis, regeneration and cancer
Peter Friedl,Darren Gilmour +1 more
TL;DR: Comparing different types of collective migration at the molecular and cellular level reveals a common mechanistic theme between developmental and cancer research.
Journal ArticleDOI
Role of platelet-derived growth factors in physiology and medicine.
TL;DR: Basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts are reviewed.
Journal ArticleDOI
Molecular regulation of angiogenesis and lymphangiogenesis.
Ralf H. Adams,Kari Alitalo +1 more
TL;DR: The angiogenic growth of blood vessels and lymphatic vessels coordinates several biological processes such as cell proliferation, guided migration, differentiation and cell–cell communication.
Journal ArticleDOI
Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis
Mats Hellström,Li-Kun Phng,Jennifer J. Hofmann,Elisabet Wallgard,Leigh Coultas,Per Lindblom,Per Lindblom,Jackelyn A. Alva,Ann Katrin Nilsson,Linda Karlsson,Nicholas Gaiano,Keejung Yoon,Janet Rossant,M. Luisa Iruela-Arispe,Mattias Kalén,Holger Gerhardt,Christer Betsholtz +16 more
TL;DR: Evidence is presented that delta-like 4 (Dll4)–Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina, and modulators of Dll4 or Notch signalling, such as γ-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
References
More filters
Journal ArticleDOI
Angiogenesis in cancer and other diseases
Peter Carmeliet,Rakesh K. Jain +1 more
TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Journal ArticleDOI
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Peter Carmeliet,Valérie Ferreira,Georg Breier,Saskia Pollefeyt,Lena Kieckens,Marina Gertsenstein,Michaela Fahrig,Ann Vandenhoeck,Kendraprasad Harpal,Carmen Eberhardt,Cathérine Declercq,Judy Pawling,Lieve Moons,Desire Collen,Werner Risau,Andras Nagy,Andras Nagy +16 more
TL;DR: It is reported that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES)16,17, and even more impaired in homozygous D1-VEGF- deficient (VDGF-/-) T-ES embryos, resulting in death at mid-gestation.
Journal ArticleDOI
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.
Fouad Shalaby,Janet Rossant,Janet Rossant,Terry P. Yamaguchi,Terry P. Yamaguchi,Marina Gertsenstein,Xiang-Fu Wu,Xiang-Fu Wu,Martin L. Breitman,Martin L. Breitman,Andre C. Schuh +10 more
TL;DR: The generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells is reported, indicating that FlK-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.
Journal ArticleDOI
Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
Donald R. Senger,Stephen J. Galli,Ann M. Dvorak,Carole A. Perruzzi,V. Susan Harvey,Harold F. Dvorak +5 more
TL;DR: Tumor ascites fluids from guinea pigs, hamsters, and mice contain activity that rapidly increases microvascular permeability, and this activity is secreted by these tumor cells and a variety of other tumor cell lines in vitro.
Journal ArticleDOI
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.
Napoleone Ferrara,Karen Carver-Moore,Helen Hsifei Chen,Mary Dowd,Lucy Lu,K. Sue O'Shea,Lyn Powell-Braxton,Kenneth J. Hillan,Mark W. Moore +8 more
TL;DR: The unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12 was reported, and angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies.