Hemangioblaszt és Érfejlődés Dr. Nagy Nándor Semmelweis Egyetem, Humánmorfológiai és Fejlődésbiológiai Intézet devbio8e-fig-15-09-1.jpg

Vasculogenesis: de novo érképződés a mezodermában 1. fázis Hemangiobalsztok-----vérszigetek 2. fázis Angioblasztok proliferációja és differenciálódása endothel sejteket eredményez 3. fázis Kapillárisképződés Angiogenesis: kapilláris képződés, erek differenciálódása, vénák, nyirokerek, artériák

Hematopoiesis and vasculogenesis closely linked -- spatially and temporally -- during embryonic development The hemangioblast Hypothetical common progenitor for hematopoietic and vascular endothelial cells hematopoietic endothelial

Primitív vérképzés a szikhólyagban Kessel és Fabian, 1985 mezoderma vérszigetek vérsejtek és erek

Growth factors Basic fibroblast growth factor (bFgf/Fgf2): essential for hemangioblast formation; synthesized in the chick embryonic chorioallantoic membrane Vascular endothelial growth factor (VEGF): induce the differentiation of angioblasts into endothelial cells; secreted by the mesenchymal cells near blood islands toward VEGF receptor (Flk1, Flt1) expressing angioblasts Angiopoietin: mediates the interaction between the endothelial cells and the pericytes (smooth muscle-like cells); receptor Tie2 mutants have defective smooth muscle association with the blood vessels

VEGF (Vascular Endothelial Growth Factor) VEGF Receptorok VEGF : az ér endothel sejtjeinek növekedését fokozza, növekedési faktor, Homodimer glycoprotein, több izoformával rendelkezik VEGFR-1 Létfontosságú az embryonális angiogenezisben. VEGFR-2 Legfontosabb VEGF receptor a tumoros érképződésben VEGFR-3 A nyirokszervek endothelsejtjeiben fordul elő. Nyirokcsomó áttétek kialakulásában játszik szerepet

Yolk sacs of a wild-type mouse and a littermate heterozygous for a loss-of-function mutation of VEGF devbio8e-fig-15-15-0.jpg

Az angiogenezisnek két fő formája van: a csírázó (sprouting) véredényképzés és az lehasadó (intususceptive) véredényképzés.

Pericytes

A Proposed Model for the Recruitment of Mesenchymal Cells to Developing Vessels Angiopoietin-1 (498 AA) is a secreted angiogenic protein that interacts with endothelial specific Tie-2 receptor. Induces tyrosine phosphorylation of Tie-2. Receptor Tie2 mutants have defective smooth muscle association with the blood vessels Regulate the endothelial cell proliferation, differentiation, and proper patterning during vasculogenesis. Angiopoietin: mediates the interaction between the endothelial cells and the pericytes (smooth muscle-like cells)

The lymphatic vessel development: lymphangiogenesis Lymphatic vasculature: drain the fluids and transport lymphocytes Lymphatic sac: original site for the lymphatic vessel growth Prox1 downregulates blood vessel-specific genes, while upregulates lymphatic vessel genes (VEGFR3, a receptor for VEGF-C (lymphatic endothelial proliferator) )

VEGF-C is critical for the formation of the lymphatic vessels Development of the lymphatic vasculature Is arrested in Prox1 mutant devbio8e-fig-15-20-0.jpg

every cell must be within 50 to 100 mm of a capillary Hypoxia - HIF - VEGF every cell must be within 50 to 100 mm of a capillary 1971 - Surgeon Dr. Judah Folkman hypothesizes that tumor growth is dependent upon angiogenesis. His theory, published in the New England Journal of Medicine, is initially regarded as heresy by leading physicians and scientists Inhibition of tumor angiogenesis HIF: hypoxia inducuble factor VEGF: vascular endothelial growth factor

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Arteries are specifically aligned with peripheral nerves in mouse limb skin devbio8e-fig-15-19-0.jpg

Intestinal vessels and enteric neurons develop in close association in zebrafish 5 dpf Tg(fli-EGFP) RED: HuC antibody (enteric neurons) GREEN: Fli-EGFP + anti-GFP antibody (blood vessels) We were interested in knowing whether a similar relationship between EC and ENCCs exists in other species. Nagy N és mtsai 2009 Developmental Biology

Model of the roles of ephrin and Eph receptors during angiogenesis devbio8e-fig-15-16-1.jpg