Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling
Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling
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.
- University of Salford United Kingdom
- University of Manchester, Faculty of Life Sciences United Kingdom
- University of Manchester
- University Of Manchester
- University of Manchester United Kingdom
Collagen Type IV, Feedback, Physiological, Integrins, Embryo, Nonmammalian, QH301-705.5, Embryonic Development, Gene Expression, Gene Expression Regulation, Developmental, Article, Cell Line, Drosophila melanogaster, Report, Bone Morphogenetic Proteins, Animals, Drosophila Proteins, Biology (General), Signal Transduction
Collagen Type IV, Feedback, Physiological, Integrins, Embryo, Nonmammalian, QH301-705.5, Embryonic Development, Gene Expression, Gene Expression Regulation, Developmental, Article, Cell Line, Drosophila melanogaster, Report, Bone Morphogenetic Proteins, Animals, Drosophila Proteins, Biology (General), Signal Transduction
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