Is Drosophila Dpp/BMP morphogen spreading required for wing patterning and growth?

Abstract

Secreted signaling molecules act as morphogens to control patterning and growth in many developing tissues. Since locally produced morphogens spread to form a concentration gradient in the surrounding tissue, spreading is generally thought to be the key step in the non‐autonomous actions. Here, we review recent advances in tool development to investigate morphogen function using the role of decapentaplegic (Dpp)/bone morphogenetic protein (BMP)‐type ligand in the Drosophila wing disc as an example. By applying protein binder tools to distinguish between the roles of Dpp spreading and local Dpp signaling, we found that Dpp signaling in the source cells is important for wing patterning and growth but Dpp spreading from this source cells is not as strictly required as previously thought. Given recent studies showing unexpected requirements of long‐range action of different morphogens, manipulating endogenous morphogen gradients by synthetic protein binder tools could shed more light on how morphogens act in developing tissues.

Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix

“…Taken together, these results indicate that specific extracellular HSPGs, but not cell-surface bound HSPGs, may directly regulate the range of Fgf8 signaling, potentially serving differing roles. Interestingly, for Dpp morphogen in the fly wing, distinct roles were recently observed in long range spreading and in local signaling at source cells, respectively [19].…”

“…During early gastrulation, the majority of Fgf8 molecules (91 %) spread in between cells by free diffusion, as was seen using Fluorescence Correlation Spectroscopy (FCS) in living zebrafish embryos, but a small fraction of the molecules (9 %) move as a slow fraction, which is dependent on extracellular heparan sulfate (HS) sugar chains [3,7]. Novel biophysical approaches to directly monitor transport at the single-molecule level have helped in quantitatively elucidating the mechanisms of transport [3,6,7,[14][15][16][17][18][19][20], but the exact interplay between free diffusion and interactions with the ECM is not clear, and the identity of molecules in the ECM which regulate Fgf8 transport in vivo is not well understood.…”