טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHarary Noga
SubjectHeparanase Involvement in Embryogenesis
DepartmentDepartment of Medicine
Supervisors Professor Israel Vlodavsky
Professor Emeritus Gera Neufeld


Abstract

Heparan sulfate proteoglycans (HSPGs) are ubiquitous macromolecules associated with the cell surface and ECM of a wide range of cells of vertebrate and invertebrate tissues. The basic HSPG structure consists of a protein core to which several linear heparan sulfate (HS) chains are covalently O-linked. Heparanase is an endo-beta-D-glucuronidase involved in cleavage of HS side chains of HSPGs, and hence participates in extracellular matrix degradation and remodeling. In the present work we first investigated heparanase expression during human development, examined at 10, 18 and 26 weeks of pregnancy. Heparanase expression was found mainly in epithelial structures, including the intestine, kidney, liver and respiratory epithelium of the trachea and lungs. In order to investigate heparanase expression throughout embryogenesis, we took the advantage of the avian model, applying immonohistochemical staining on chick and quail embryos at different developmental stages. Heparanase was specifically expressed in endothelial cells of all blood vessels, including the heart endothelium, liver sinusoids, and lymphatics, throughout embryogenesis and up to 10 days postnatal. In Xenopus embryos, heparanase ectopic expression induced gastrulation defects, inhibition of DLMZ (Dorsal Latheral Marginal Zone) elongation and reduction in muscle actin mRNA levels. BMP4 is a signaling factor involved in neurogenesis and in mesoderm formation. In this study we show that one mechanism by which heparanase may affect gastrulation is by causing inappropriate BMP4 distribution in the embryo. We propose that interference with BMP4 signaling is a potential way by which heparanase activity affects gastrulation or embryogenic progression.