Neuronal migration is a fundamental process during the development of the 
cerebral cortex and is regulated by cytoskeletal components. Microtubule 
dynamics can be modulated by posttranslational modifications to tubulin 
subunits. Acetylation of α-tubulin at lysine 40 is important in regulating 
microtubule properties, and this process is controlled by acetyltransferase and 
deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has 
been found to play a major role in the acetylation of α-tubulin in different 
species in vivo. However, the physiological function of MEC-17 during neural 
development is largely unknown. Here, we report that MEC-17 is critical for the 
migration of cortical neurons in the rat. MEC-17 was strongly expressed in the 
cerebral cortex during development. MEC-17 deficiency caused migratory defects 
in the cortical projection neurons and interneurons, and perturbed the 
transition of projection neurons from the multipolar stage to the 
unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, 
knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to 
mimic acetylated α-tubulin could reduce the migratory and morphological defects 
caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which 
regulates the acetylation of α-tubulin, appears to control the migration and 
morphological transition of cortical neurons. This finding reveals the 
importance of MEC-17 and α-tubulin acetylation in cortical development.