1. The GTPase Rab8 differentially controls the long- and short-range activity of the Hedgehog morphogen gradient by regulating Hedgehog apico-basal distribution.
- Author
-
Gore T, Matusek T, D'Angelo G, Giordano C, Tognacci T, Lavenant-Staccini L, Rabouille C, and Thérond PP
- Subjects
- Animals, Animals, Genetically Modified metabolism, Drosophila Proteins antagonists & inhibitors, Drosophila Proteins genetics, Endocytosis, Endosomes metabolism, GTP Phosphohydrolases antagonists & inhibitors, GTP Phosphohydrolases genetics, Gene Expression Regulation, Hedgehog Proteins genetics, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mutagenesis, Protein Stability, RNA Interference, RNA, Double-Stranded metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Signal Transduction, Drosophila metabolism, Drosophila Proteins metabolism, GTP Phosphohydrolases metabolism, Hedgehog Proteins metabolism
- Abstract
The Hedgehog (Hh) morphogen gradient is required for patterning during metazoan development, yet the mechanisms involved in Hh apical and basolateral release and how this influences short- and long-range target induction are poorly understood. We found that depletion of the GTPase Rab8 in Hh-producing cells induces an imbalance between the level of apically and laterally released Hh. This leads to non-cell-autonomous differential effects on the expression of Hh target genes, namely an increase in its short-range targets and a concomitant decrease in long-range targets. We further found that Rab8 regulates the endocytosis and apico-basal distribution of Ihog, a transmembrane protein known to bind to Hh and to be crucial for establishment of the Hh gradient. Our data provide new insights into morphogen gradient formation, whereby morphogen activity is functionally distributed between apically and basolaterally secreted pools., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)
- Published
- 2021
- Full Text
- View/download PDF