Dpp dispersal in the Drosophila melanogaster wing disc

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta
(TGF-β) superfamily and have been shown to be important for many developmental processes
(Balemans & Van Hul, 2002; Shi & Massagué, 2003). In the fruit fly Drosophila melanogaster,
many investigations focus on the BMP2/4 orthologue Decapentaplegic (Dpp). In the
Drosophila wing imaginal disc, Dpp is secreted in an anterior stripe at the anterior/posterior
compartment border and disperses to form a concentration gradient (Lecuit et al., 1996). This
gradient is disturbed in mutants encoding Heparan Sulfate (HS) modifying enzymes, such as
Sulfateless (Sulf) (Belenkaya et al., 2004) and Sugarless (Sgl) (Bornemann et al., 2004). HS
chains are part of the Heparan Sulfate Proteogylcans (HSPGs) and important for their function.
In the Drosophila wing imaginal disc, two glypicans, Division abnormally delayed (Dally) and
Dally-like (Dlp) are present on the cell surface. Both have been demonstrated to be important
for morphogen function, however, how the distinct glypicans control Dpp distribution and
signaling through HS remains largely unknown. In the present study, the roles of the glypicans
for Dpp function was analyzed by classical means and extended by novel approaches.
I first found that, although glypicans are modified by HS, only Dally is required for Dpp gradient
formation and signaling through interaction of its core protein with Dpp. I then found that
Dally is largely dispensable for transporting or recycling of Dpp, but it is required for Dpp
stability on the cell surface through antagonizing Tkv-mediated internalization trough the HS
chains. Interestingly I found that direct interaction of Dally and Dpp appears to be largely
dispensable.
Taken together, these result provide new insights into how glypicans control morphogen
functions during development.