The roles of microtubule-associated proteins in brain morphogenesis: a review

Microtubule-associated proteins (MAPs) are a diverse family of cytoskeletal proteins that copurify with tubulin in vitro. Recently a number of novel approaches have been used to learn more about the functions of MAPs during brain development, including: localization of MAPs and their mRNA in the developing brain, comparisons of MAPs between species to learn potential fundamental characteristics, biochemical analysis of changes in MAPs in process-bearing cell lines, and sequence analysis of MAP cDNAs and cDNA transfection studies. Taken together, these data allow us to assign roles to MAPs which are abundant in the developing brain, and to develop models for future studies. Four MAPs are particularly abundant in the developing brain: MAP1B, the high and low-molecular weight forms of MAP2, and juvenile tau. MAP1B is the only MAP to be found consistently in extending processes in both the developing and adult brain, making it a likely regulator of neurite outgrowth. High-molecular weight MAP2 and tau crosslink microtubules in dendrites and axons, respectively. Low-molecular weight MAP2 may be able to regulate MAP2-mediated crosslinking to make processes more labile during development and in adult brain regions where synaptogenesis is active. Tau-mediated crosslinking may be regulated by temporal regulation of the expression of tau forms with different binding affinities to tubulin. High-molecular weight MAP2 is sequestered into dendrites by the selective transport of its mRNA. This allows rapid and local regulation of MAP2 synthesis.