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First published online July 23, 2007
doi: 10.1242/10.1242/jcs.003590

Journal of Cell Science 120, 2507-2516 (2007)
Published by The Company of Biologists 2007
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Research Article

Neurotrophic factors switch between two signaling pathways that trigger axonal growth

Mikhail Paveliev1,*, Maria Lume1, Agne Velthut1, Matthew Phillips1,2, Urmas Arumäe1 and Mart Saarma1,*

1 Institute of Biotechnology, University of Helsinki, Helsinki FIN-00014, Finland
2 Division of Signal Transduction, Harvard Medical School, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, 10th Floor, Boston, MA 02115, USA

* Authors for correspondence (e-mail: Mikhail.Paveliev{at}helsinki.fi; Mart.Saarma{at}helsinki.fi)

Accepted 24 May 2007

Integration of multiple inputs from the extracellular environment, such as extracellular matrix molecules and growth factors, is a crucial process for cell function and information processing in multicellular organisms. Here we demonstrate that co-stimulation of dorsal root ganglion neurons with neurotrophic factors (NTFs) – glial-cell-line-derived neurotrophic factor, neurturin or nerve growth factor – and laminin leads to axonal growth that requires activation of Src family kinases (SFKs). A different, SFK-independent signaling pathway evokes axonal growth on laminin in the absence of the NTFs. By contrast, axonal branching is regulated by SFKs both in the presence and in the absence of NGF. We propose and experimentally verify a Boolean model of the signaling network triggered by NTFs and laminin. Our results demonstrate that NTFs provide an environmental cue that triggers a switch between separate pathways in the cell signaling network.

Key words: Boolean networks, Src family kinases, Axonal growth, Neurotrophic factors






© The Company of Biologists Ltd 2007