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

果蝇表皮生长因子受体通路调节 Hedgehog 信号和细胞丝行为

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作者: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, Isabel Guerrero

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.

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