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Updated: May 3, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation

Christelle Forcet1, Elke Stein, Laurent Pays

  • 1Apoptosis/Differentiation Laboratory label 'La Ligue' Molecular and Cellular Genetic Center, CNRS UMR 5534, University of Lyon, 69622 Villeurbanne, France.

Nature
|May 3, 2002
PubMed

Insights

Netrin-1 guides developing axons via Deleted in colorectal cancer (Dcc) receptors. This study reveals Dcc activates mitogen-activated protein kinase (MAPK) signaling, crucial for axon growth and guidance.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Neuronal growth cones navigate using guidance cues.
  • Netrin-1 is a key bifunctional cue in mammals, mediating both attraction and repulsion.
  • The Deleted in colorectal cancer (Dcc) receptor mediates netrin-1's attractive effects, but its signaling pathways are unclear.

Purpose of the Study:

  • To elucidate the signaling mechanisms by which Dcc mediates netrin-1's chemoattractive effects on commissural axons.
  • To investigate the role of mitogen-activated protein kinase (MAPK) signaling in Dcc-mediated axon guidance.

Main Methods:

  • Utilized transfected cells and primary commissural neurons.
  • Investigated the activation of extracellular signal-regulated kinase (ERK)-1 and -2 upon netrin-1 binding to Dcc.
  • Examined the recruitment of ERK-1/2 to the Dcc receptor complex.
  • Assessed the impact of ERK-1/2 inhibition on netrin-dependent axon outgrowth and orientation.

Main Results:

  • Netrin-1 binding to Dcc activates mitogen-activated protein kinase (MAPK) signaling, specifically ERK-1 and -2.
  • ERK-1/2 activation is linked to its recruitment into a Dcc receptor complex.
  • Inhibiting ERK-1/2 signaling significantly impairs netrin-dependent axon outgrowth and directional guidance.

Conclusions:

  • Dcc receptor activation by netrin-1 triggers MAPK/ERK signaling.
  • MAPK signaling, mediated by ERK-1/2 recruitment to Dcc, is essential for netrin-1's role in axon growth and guidance.

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