Abstract
Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length. EGFR regulates the organisation of endosomes in which Crb and Serp proteins are loaded. Our results are consistent with a role of EGFR in regulating Retromer/WASH recycling routes. Furthermore, we provide new insights into Crb trafficking and recycling during organ formation. Our work connects cell signalling, trafficking mechanisms and morphogenesis and suggests that the regulation of cargo trafficking can be a general outcome of EGFR activation.
Highlights
Understanding how organs form and are maintained is a major goal in developmental biology
Tracheal system development represents an excellent system to study the molecular mechanisms employed by signalling pathways to instruct cells to form tubular structures
We find that Epidermal Growth Factor Receptor (EGFR) regulates the accumulation and subcellular localisation of Crumbs and Serpentine, two factors previously known to regulate tube length
Summary
Understanding how organs form and are maintained is a major goal in developmental biology. Diametric/circumferential growth of tracheal tubes occurs at stage 14 and correlates with a pulse of secretion that ensures apical membrane growth and secretion of contents into the lumen [4,6] This secreted luminal material, which includes chitin, chitin-associated proteins and ZP proteins like Pio-Pio and Dumpy, forms an apical extracellular matrix (aECM) that organises into an elastic filament [7,8]. Longitudinal/axial growth of tracheal tubes occurs in a continuous manner after diametric expansion It depends on intrinsic cell properties such as Crumbs-dependant (Crb) apical membrane growth [7,11] and pSrc-dependant polarised cell shape changes [12,13]. While we have some hints into how these intrinsic cell properties and the aECM crosstalk and are balanced to control the final tube size [7,16] we still don’t have a complete picture of how it works
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