The Drosophila epidermal growth factor receptor pathway regulates Hedgehog signalling and cytoneme behaviour

Vasiliki S. Lalioti, Ana-Citlali Gradilla, Carlos Jiménez-Jiménez, Clara Fernández-Pardo, David Sánchez-Hernández, Adrián Aguirre-Tamaral, Irene Sánchez-Platero, Sheila Jordán-Àlvarez, James G. Wakefield and Isabel Guerrero (iguerrero@cbm.csic.es)
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Vasiliki S. Lalioti: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Ana-Citlali Gradilla: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Carlos Jiménez-Jiménez: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Clara Fernández-Pardo: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
David Sánchez-Hernández: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Adrián Aguirre-Tamaral: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Irene Sánchez-Platero: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
Sheila Jordán-Àlvarez: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid
James G. Wakefield: University of Exeter
Isabel Guerrero: Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract During Drosophila epithelial development, dynamic signalling filopodia (cytonemes) establish direct contacts between distant cells to facilitate the formation of the Hedgehog signalling gradient. However, not much is known about how cytonemes are regulated. In this study, we show that cytoneme dynamics and Hedgehog signalling in the Drosophila epithelia depend on the Epidermal Growth Factor pathway and on its downstream effector Ras1. We describe that EGFR/Ras1 pathway is required to maintain in the wing disc epithelium the basal plasma membrane levels of Interference Hedgehog (Ihog), a critical Hh co-receptor and adhesion protein. In addition, our data demonstrate that filamin A or Cheerio in Drosophila, responds to both Ihog and EGFR pathway and recruited to the basal site of the plasma membrane. This recruitment contributes to Ihog’s role in stabilizing cytonemes.

Date: 2025
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DOI: 10.1038/s41467-025-57162-5

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