Glypicans define unique roles for the Hedgehog co-receptors Boi and Ihog in cytoneme-mediated gradient formation
- Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Spain
- Growth and Development, Biozentrum, University of Basel, Switzerland
Abstract
The conserved family of Hedgehog (Hh) signaling proteins plays a key role in cell-cell communication during development, tissue repair and cancer progression, inducing distinct concentration-dependent responses in target cells located at short and long distances. One simple mechanism for long distance dispersal of the lipid modified Hh is the direct contact between cell membranes through filopodia-like structures known as cytonemes. Here we have analyzed in Drosophila the interaction between the glypicans Dally and Dally-like protein, necessary for Hh signaling, and the adhesion molecules and Hh coreceptors Ihog and Boi. We describe that glypicans are required to maintain the levels of Ihog, but not of Boi. We also show that the overexpression of Ihog, but not of Boi, regulates cytoneme dynamics through their interaction with glypicans, the Ihog fibronectin III domains being essential for this interaction. Our data suggest that the regulation of glypicans over Hh signaling is specifically given by their interaction with Ihog in cytonemes. Contrary to previous data, we also show that there is no redundancy of Ihog and Boi functions in Hh gradient formation, being Ihog, but not of Boi, essential for the long-range gradient.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Ministerio de Ciencia, Innovación y Universidades (BFU2014-59438-P)
- Eleanor Simon
- Irene Seijo-Barandiarán
- Gustavo Aguilar
- David Sánchez-Hernández
- Adrián Aguirre
- Laura González-Méndez
- Isabel Guerrero
Ministerio de Ciencia, Innovación y Universidades (BFU2017-83789-P)
- Eleanor Simon
- Carlos Jiménez-Jiménez
- David Sánchez-Hernández
- Laura González-Méndez
- Pedro Ripoll
- Isabel Guerrero
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Steffen Scholpp, University of Exeter, United Kingdom
Version history
- Received: November 3, 2020
- Accepted: August 4, 2021
- Accepted Manuscript published: August 6, 2021 (version 1)
- Version of Record published: September 1, 2021 (version 2)
Copyright
© 2021, Simon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Glypicans define unique roles for the Hedgehog co-receptors Boi and Ihog in cytoneme-mediated gradient formation
eLife 10:e64581.
https://doi.org/10.7554/eLife.64581
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