MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance

Curr Biol. 2004 May 25;14(10):840-50. doi: 10.1016/j.cub.2004.04.046.


Background: The signaling cascades governing neuronal migration and axonal guidance link extracellular signals to cytoskeletal components. MAP1B is a neuron-specific microtubule-associated protein implicated in the crosstalk between microtubules and actin filaments.

Results: Here we show that Netrin 1 regulates, both in vivo and in vitro, mode I MAP1B phosphorylation, which controls MAP1B activity, in a signaling pathway that depends essentially on the kinases GSK3 and CDK5. We also show that map1B-deficient neurons from the lower rhombic lip and other brain regions have reduced chemoattractive responses to Netrin 1 in vitro. Furthermore, map1B mutant mice have severe abnormalities, similar to those described in netrin 1-deficient mice, in axonal tracts and in the pontine nuclei.

Conclusions: These data indicate that MAP1B phosphorylation is controlled by Netrin 1 and that the lack of MAP1B impairs Netrin 1-mediated chemoattraction in vitro and in vivo. Thus, MAP1B may be a downstream effector in the Netrin 1-signaling pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Blotting, Western
  • Brain / embryology
  • Brain / metabolism*
  • Cell Line
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Glycogen Synthase Kinase 3 / metabolism
  • Histological Techniques
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Microtubule-Associated Proteins / metabolism*
  • Microtubule-Associated Proteins / physiology
  • Nerve Growth Factors / metabolism*
  • Nerve Growth Factors / physiology
  • Netrin-1
  • Neurons / physiology*
  • Phosphorylation
  • Signal Transduction / physiology*
  • Tumor Suppressor Proteins


  • Microtubule-Associated Proteins
  • Nerve Growth Factors
  • Ntn1 protein, mouse
  • Tumor Suppressor Proteins
  • microtubule-associated protein 1B
  • Netrin-1
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse
  • Cyclin-Dependent Kinases
  • Glycogen Synthase Kinase 3