Journal
DEVELOPMENT
Volume 141, Issue 16, Pages 3233-3242Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.106039
Keywords
Drosophila; Human; Mouse; Glial cell migration; PVR; PDGF-receptor; Lysyl oxidase; Lox; Extracellular matrix
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [Pa 328/7-1, SFB 629 B6]
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Cell migration is an important feature of glial cells. Here, we used the Drosophila eye disc to decipher the molecular network controlling glial migration. We stimulated glial motility by pan-glial PDGF receptor (PVR) activation and identified several genes acting downstream of PVR. Drosophila lox is a non-essential gene encoding a secreted protein that stiffens the extracellular matrix (ECM). Glial-specific knockdown of Integrin results in ECM softening. Moreover, we show that lox expression is regulated by Integrin signaling and vice versa, suggesting that a positive-feedback loop ensures a rigid ECM in the vicinity of migrating cells. The general implication of this model was tested in a mammalian glioma model, where a Lox-specific inhibitor unraveled a clear impact of ECM rigidity in glioma cell migration.
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