The role of glycosaminoglycan modification in Hedgehog regulated tissue morphogenesis.

ABSTRACT

Patterns of gene expression, cell growth and cell-type specification during development are often regulated by morphogens. Morphogens are signalling molecules produced by groups of source cells located tens to hundreds of micrometers distant from the responding tissue and are thought to regulate the fate of receiving cells in a direct, concentration-dependent manner. The mechanisms that underlie scalable yet robust morphogen spread to form the activity gradient, however, are not well understood and are currently intensely debated. Here, based on two recent publications, we review two in vivo derived concepts of regulated gradient formation of the morphogen Hedgehog (Hh). In the first concept, Hh disperses on the apical side of developing epithelial surfaces using the same mechanistic adaptations of molecular transport that DNA-binding proteins in the nucleus use. In the second concept, Hh is actively conveyed to target cells via long filopodial extensions, called cytonemes. Both concepts require the expression of a family of sugar-modified proteins in the gradient field called heparan sulphate proteoglycans as a prerequisite for Hh dispersal, yet propose different - direct versus indirect - roles of these essential extracellular modulators.