Abstract
SummaryWithin 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.
Highlights
Two key requirements for the success of multicellular life are the ability of cells to adhere to each other, via a secreted protein network called the extracellular matrix (ECM), and to communicate with each other, sometimes over long distances, through the release of signaling molecules
We find that maximal levels of bone morphogenetic proteins (BMPs) pathway activation in vivo are only achieved in the presence of integrin signaling, which functions downstream of collagen IV to potentiate signaling through the canonical Smad pathway
Integrins Are Required for Peak Levels of BMP Signaling in the Early Drosophila Embryo We examined a role for integrins in BMP pathway activation in the early Drosophila embryo, where a BMP activity gradient specifies cell fates along the dorsoventral axis (Figure 1A)
Summary
Cells receive information from the extracellular matrix via integrin receptors, in addition to growth factor signals from other cells. Sawala et al show that BMP-responsive transcription in the Drosophila embryo is not a readout of the BMP concentration and requires integrinmediated enhancement of BMP signal transduction. Highlights d Drosophila embryos lacking integrin function have disrupted BMP responses d Collagen IV activates integrin signaling to enhance levels of the pMad transducer d Integrins bind BMP receptors and promote pMad levels after BMP receptor activation d BMP activates expression of an a-integrin, representing a positive feedback loop.
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