Handling Editor: Patrick Tam
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: P.P.T., T.M.; Methodology: T.M.; Validation: P.P.T., T.M., T.G., G.D., C.G., L.L.-S.; Formal analysis: P.P.T., T.M., T.G., G.D., C.G.; Investigation: T.M., T.G., G.D., C.G., T.T., L.L.-S.; Resources: P.P.T.; Data curation: T.M.; Writing - original draft: P.P.T.; Writing - review & editing: P.P.T., T.M., C.R.; Supervision: P.P.T., T.M.; Project administration: P.P.T.; Funding acquisition: P.P.T.
Funding
T.G. held an AXA Research Fund and Fondation ARC pour la Recherche sur le Cancer fellowship, C.G. held a Fondation ARC pour la Recherche sur le Cancer fellowship. This work was supported by grants from Ligue Contre le Cancer ‘Equipe labellisée 2016’, the LABEX SIGNALIFE (ANR-11-LABX-0028-01) and the Agence Nationale de la Recherche (ANR-15-CE13-0002-01) to P.P.T.
Supplementary information
Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.191791.supplemental
- Received April 22, 2020.
- Accepted January 19, 2021.
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