Dally is not essential for Dpp spreading or internalization but for Dpp stability by antagonizing Tkv-mediated Dpp...

Area of Science:

• Developmental Biology
• Molecular Biology
• Cell Biology

Background:

• Heparan sulfate proteoglycans (HSPGs) are key cell-surface molecules regulating morphogen gradient formation and signaling.
• In Drosophila wing discs, glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) were thought to redundantly control Dpp morphogen gradients via their heparan sulfate (HS) chains.
• Previous models proposed glypicans facilitate or hinder Dpp spreading, stabilize Dpp, or recycle Dpp, but distinct HSPG functions remained unclear.

Purpose of the Study:

• To elucidate the distinct roles of Dally and Dlp in controlling Dpp morphogen gradient formation and signaling in Drosophila wing discs.
• To investigate the specific contributions of Dally's core protein and HS chains to Dpp gradient regulation.

Main Methods:

• Generation of genome-engineered platforms for Dally and Dlp in Drosophila.
• Analysis of Dally and Dlp function in Dpp gradient formation and signaling.
• Investigation of Dally-Dpp and Dally HS-Dpp interactions.

Main Results:

• Only Dally, not Dlp, was found to be critical for Dpp gradient formation and signaling.
• Dally's core protein interacts with Dpp, but this interaction alone is insufficient for function.
• Dally's HS chains are essential for Dpp gradient formation and signaling, primarily by stabilizing Dpp on the cell surface.
• Dally's HS chains antagonize receptor-mediated Dpp internalization, rather than facilitating Dpp spreading or recycling.

Conclusions:

• Dally plays a critical, non-redundant role in Dpp morphogen gradient control in the Drosophila wing disc.
• Dally regulates Dpp signaling through a dual mechanism involving its core protein and HS chains.
• HS chains of Dally stabilize Dpp by inhibiting its internalization, providing a novel mechanism for morphogen gradient regulation.