title: Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling.
abstract: Within a 3D tissue, cells need to integrate signals from growth factors, such as BMPs, and the extracellular matrix (ECM) to coordinate growth and differentiation. Here, we use the Drosophila embryo as a model to investigate how BMP responses are influenced by a cell's local ECM environment. We show that integrins, which are ECM receptors, are absolutely required for peak BMP signaling. This stimulatory effect of integrins requires their intracellular signaling function, which is activated by the ECM protein collagen IV. Mechanistically, integrins interact with the BMP receptor and stimulate phosphorylation of the downstream Mad transcription factor. The BMP-pathway-enhancing function of integrins is independent of focal adhesion kinase, but it requires conserved NPXY motifs in the β-integrin cytoplasmic tail. Furthermore, we show that an α-integrin subunit is a BMP target gene, identifying positive feedback between integrin signaling and BMP pathway activity that may contribute to robust cell fate decisions.
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Annick
authors: A
authors: Sawala
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Margherita
authors: M
authors: Scarcia
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Catherine
authors: C
authors: Sutcliffe
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Scott G
authors: SG
authors: Wilcockson
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: hilary.ashe@manchester.ac.uk.
authors: Hilary L
authors: HL
authors: Ashe
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D025461:Feedback, Physiological; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D016023:Integrins / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; D024141:Collagen Type IV; D029721:Drosophila Proteins; D016023:Integrins