Development. 2021 Mar 9;148(5):dev191791. doi: 10.1242/dev.191791.
Tanvi Gore 1, Tamás Matusek 1, Gisela D’Angelo 1 2, Cécile Giordano 1 2, Thomas Tognacci 1, Laurence Lavenant-Staccini 1, Catherine Rabouille 3 4, Pascal P Thérond 5
1 Université Côte d’Azur, UMR7277 CNRS, Inserm 1091, Institut de Biologie de Valrose (iBV), Parc Valrose, 06108 Nice cedex2, France.
2 Institut Curie, UMR144 CNRS, 12 Rue Lhomond, 75005 Paris, France.
3 Department of Cell Biology, Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences & University Medical Center Utrecht, 3584 CT Utrecht, Netherlands.
4 Department of Biomedical Science of Cells and Systems, University Medical Center Groningen, 9700 AD Groningen, Netherlands.
5 Université Côte d’Azur, UMR7277 CNRS, Inserm 1091, Institut de Biologie de Valrose (iBV), Parc Valrose, 06108 Nice cedex2, France email@example.com.
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.