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The Journal of Neuroscience, August 11, 2004, 24(32):7204-7213; doi:10.1523/JNEUROSCI.2254-04.2004
 Previous Article
Development/Plasticity/Repair
Microtubule-Associated Protein 1B Controls Directionality of Growth Cone Migration and Axonal Branching in Regeneration of Adult Dorsal Root Ganglia Neurons
Céline Bouquet,1
Sylvia Soares,1
Ysander von Boxberg,1
Michèle Ravaille-Veron,1
Friedrich Propst,2 and
Fatiha Nothias1
1Unité Mixte de Recherche 7101, Centre National de la Recherche Scientifique-Université Pierre et Marie Curie, Laboratory Neurobiologie des Signaux Intercellulaires, Institut Fédératif de Recherche-Biologie Intégrative, Université Pierre et Marie Curie, 75005 Paris, France, and 2Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, University of Vienna, A-1030 Vienna, Austria
During development, microtubule-associated protein 1B (MAP1B) is one of the earliest MAPs, preferentially localized in axons and growth cones, and plays a role in axonal outgrowth. Although generally downregulated in the adult, we have shown that MAP1B is constitutively highly expressed in adult dorsal root ganglia (DRGs) and associated with central sprouting and peripheral regeneration of these neurons. Mutant mice with a complete MAP1B null allele that survive until adulthood exhibit a reduced myelin sheath diameter and conductance velocity of peripheral axons and lack of the corpus callosum. Here, to determine the function of MAP1B in axonal regeneration, we used cultures of adult DRG explants and/or dissociated neurons derived from this map1b-/- mouse line. Whereas the overall length of regenerating neurites lacking MAP1B was similar to wild-type controls, our analysis revealed two main defects. First, map1b-/- neurites exhibited significantly (twofold) higher terminal and collateral branching. Second, the turning capacity of growth cones (i.e., "choice" of a proper orientation) was impaired. In addition, lack of MAP1B may affect the post-translational modification of tubulin polymers: quantitative analysis showed a reduced amount of acetylated microtubules within growth cones, whereas the distribution of tyrosinated or detyrosinated microtubules was normal. Both growth cone turning and axonal branch formation are known to involve local regulation of the microtubule network. Our results demonstrate that MAP1B plays a role in these processes during plastic changes in the adult. In particular, the data suggest MAP1B implication in the locally coordinated assembly of cytoskeletal components required for branching and straight directional axon growth.
Key words: microtubule-associated protein 1B; dorsal root ganglia; microtubules; MAP1B knock-out; axonal stability; growth cone turning; axonal spreading; outgrowth
Received Jan 19, 2004;
accepted June 23, 2004.
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