Evidence for the role of MAP1B in axon formation

Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation.This work was supported by grants from the Spanish Direccion General de Investigacion Cientifica y Tecnica, Comunidad de Madrid, European Union, and an institutional grant from Formation de Recherche Associee to J.A. It was also supported by grants from Consejo Nacional de Investigaciones Cientificas y Tecnicas de Argentina (PICT-PIP 4906), FONCyT (PICT 05-00000-00937 and 99-5-6179), CONICOR, and a Howard Hughes Medical Institute Grant (HMMI 75197-553201) awarded under the International Research Scholars Program to A.C. An A.E.C.I./I.C.I. predoctoral fellowship was awarded to C.G.-B. The MAP1B mutant mouse was generated with financial support from Amgen and the Max Planck Society in the laboratory of Prof. P. Gruss.Peer reviewe