Scribbled Optimizes BMP Signaling through Its Receptor Internalization to the Rab5 Endosome and Promote Robust Epithelial Morphogenesis.
Epithelial cells are characterized by apical-basal polarity. Intrinsic factors underlying apical-basal polarity are crucial for tissue homeostasis and have often been identified to be tumor suppressors. Patterning and differentiation of epithelia are key processes of epithelial morphogenesis and are frequently regulated by highly conserved extrinsic factors. However, due to the complexity of morphogenesis, the mechanisms of precise interpretation of signal transduction as well as spatiotemporal control of extrinsic cues during dynamic morphogenesis remain poorly understood. Wing posterior crossvein (PCV) formation in Drosophila serves as a unique model to address how epithelial morphogenesis is regulated by secreted growth factors. Decapentaplegic (Dpp), a conserved bone morphogenetic protein (BMP)-type ligand, is directionally trafficked from longitudinal veins (LVs) into the PCV region for patterning and differentiation. Our data reveal that the basolateral determinant Scribbled (Scrib) is required for PCV formation through optimizing BMP signaling. Scrib regulates BMP-type I receptor Thickveins (Tkv) localization at the basolateral region of PCV cells and subsequently facilitates Tkv internalization to Rab5 endosomes, where Tkv is active. BMP signaling also up-regulates scrib transcription in the pupal wing to form a positive feedback loop. Our data reveal a unique mechanism in which intrinsic polarity genes and extrinsic cues are coupled to promote robust morphogenesis.
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Jinghua
J
Gui
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Yunxian
http://orcid.org/0000-0002-6442-4406
Y
Huang
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Osamu
http://orcid.org/0000-0001-6341-9130
O
Shimmi
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins; D009024:Morphogenesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics*
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; C064196:dpp protein, Drosophila; C090169:tkv protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D052004:Bone Morphogenetic Protein Receptors; C586289:Rab5 protein, Drosophila; D020696:rab5 GTP-Binding Proteins