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Development. 2014 Aug;141(16):3233-42. doi: 10.1242/dev.106039. Epub 2014 Jul 25.

ECM stiffness regulates glial migration in Drosophila and mammalian glioma models.

Author information

1
Institute of Neurobiology, University of Münster, Münster 48149, Germany.
2
Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
3
Institute of Neurobiology, University of Münster, Münster 48149, Germany Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
4
Institute of Physiology II, University Hospital Münster, Münster 48149, Germany.
5
Department of Clinical Radiology, University Hospital Münster, Münster 48149, Germany.
6
Institute of Neurobiology, University of Münster, Münster 48149, Germany klaembt@uni-muenster.de.

Abstract

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.

KEYWORDS:

Drosophila; Extracellular matrix; Glial cell migration; Human; Lox; Lysyl oxidase; Mouse; PDGF-receptor; PVR

PMID:
25063458
DOI:
10.1242/dev.106039
[Indexed for MEDLINE]
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