Egfr is essential for maintaining epithelial integrity during tracheal remodelling in Drosophila.
A fundamental requirement during organogenesis is to preserve tissue integrity to render a mature and functional structure. Many epithelial organs, such as the branched tubular structures, undergo a tremendous process of tissue remodelling to attain their final pattern. The cohesive properties of these tissues need to be finely regulated to promote adhesion yet allow flexibility during extensive tissue remodelling. Here, we report a new role for the Egfr pathway in maintaining epithelial integrity during tracheal development in Drosophila. We show that the integrity-promoting Egfr function is transduced by the ERK-type MAPK pathway, but does not require the downstream transcription factor Pointed. Compromising Egfr signalling, by downregulating different elements of the pathway or by overexpressing the Mkp3 negative regulator, leads to loss of tube integrity, whereas upregulation of the pathway results in increased tissue stiffness. We find that regulation of MAPK pathway activity by Breathless signalling does not impinge on tissue integrity. Egfr effects on tissue integrity correlate with differences in the accumulation of markers for cadherin-based cell-cell adhesion. Accordingly, downregulation of cadherin-based cell-cell adhesion gives rise to tracheal integrity defects. Our results suggest that the Egfr pathway regulates maintenance of tissue integrity, at least in part, through the modulation of cell adhesion. This finding establishes a link between a developmental pathway governing tracheal formation and cell adhesiveness.
Cela
Carolina
C
Institut de Biologia Molecular de Barcelona (IBMB Samitier 1-5, 08028 Barcelona, Spain.
Llimargas
Marta
M
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015536:Down-Regulation; D004330:Drosophila / Q000166:cytology / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054642:Dual Specificity Phosphatase 6; D004848:Epithelium / Q000196:embryology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation; D038081:Organogenesis / Q000235:genetics; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014132:Trachea / Q000196:embryology*; D014158:Transcription, Genetic
D015820:Cadherins; D029721:Drosophila Proteins; D017468:Receptors, Fibroblast Growth Factor; D018010:Receptors, Invertebrate Peptide; C501889:shg protein, Drosophila; D011494:Protein Kinases; C102301:BTL protein, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D054642:Dual Specificity Phosphatase 6; C486844:Mkp3 protein, Drosophila; D017027:Protein Tyrosine Phosphatases