The role of Sulf1 during Sonic hedgehog mediated neural patterning

Heparan sulphate proteoglycans (HSPGs) are large molecules distributed ubiquitously, both at the cell surface and within the extracellular matrix. These molecules are known to play essential roles in developmental cell signalling, and the differential sulfation of HSPG chains gives rise to a high degree of variability in their binding specificity.
Sulf1, an N-acetlyglucosamine O-6 endosulfatase, specifically removes sulphate groups from HSPG chains in regions of high sulfation, and removal of these groups by Sulf1 leads to the attenuation of both BMP and FGF signalling.
The expression profile of Sulf1 within the neural tube of X. tropicalis is similar to that of Sonic Hedgehog (Shh) and work in both chick and Drosophila has shown that Sulf1 is able to modify the distribution of hedgehog proteins during development. Taken together, this suggests that Sulf1 may act within the ventral neural tube to modify the distribution and activity of Shh and so regulate vertebrate neural patterning.
Using the paradigm of dorsoventral patterning within the vertebrate neural tube, this thesis establishes a role for Sulf1 in modulating the distribution and activity of Shh, and demonstrates that this regulation is an important factor during neural development.