Regulated delivery controls Drosophila Hedgehog, Wingless and Decapentaplegic signaling

Abstract

Morphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc, and found that delivery to targets is regulated. Cells take up <5% Hh produced, and neither amounts taken up nor extent of signaling changes under conditions of Hh production from 50-200% normal amounts. Similarly, cells take up <25% Wg produced, and variation in Wg production from 50-700% normal has no effect on amounts taken up or signaling. Similar properties were observed for Dpp. Wing disc-produced Hh signals to disc-associated tracheal and myoblast as well as an approximately equal number of disc cells, but the extent of signaling in the disc is unaffected by the presence or absence of the tracheal cells and myoblasts. These findings show that target cells do not take up signaling proteins from a common pool and that both the amount and destination of delivered morphogens are regulated..SummaryThe extent of Hh, Wg, and Dpp signaling is independent of the amount of signal produced or the number of recipient cells.

Improving the understanding of cytoneme-mediated morphogen gradients by in silico modeling

“…This hypothesis has been recently corroborated experimentally for several morphogens. The analysis of Hh, Wg, and Dpp dispersion in the Drosophila wing imaginal disc indicates that their delivery to target cells must be regulated, since an increment in their gene doses does not alter the extent or shape of their gradients [58]. For Hh signaling, the receiving cells take up less than the 5% of Hh produced; under conditions of Hh production up to 200% of the normal amount, neither the protein uptake nor the extent of the gradient changes.…”

Improving the understanding of cytoneme-mediated morphogen gradients byin silicomodeling

“…This hypothesis has been recently corroborated experimentally for several morphogens. The analysis of the dispersion of Hh, Wg, and Dpp in the Drosophila wing imaginal disc indicates that their delivery to target cells is regulated since an increment in their gene doses does not alter the extent or shape of their gradients (48). For Hh signaling, the receiving cells take up less than the 5% of Hh produced and under conditions of Hh production up to 200% of the normal amount, neither the protein uptake nor the extent of the gradient changes.…”