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.
