Distinct α- and β-tubulin isotypes are required for the positioning, differentiation and survival of neurons: new support for the ‘multi-tubulin’ hypothesis

Synopsis The many functions of the microtubule cytoskeleton are essential for shaping the development and maintaining the operation of the nervous system. With the recent discovery of congenital neurological disorders that result from mutations in genes that encode different αand β-tubulin isotypes (TUBA1A, TUBB2B, TUBA8 and TUBB3), scientists have a novel paradigm to assess how select perturbations in microtubule function affect a range of cellular processes in humans. Moreover, important phenotypic distinctions found among the syndromes suggest that different tubulin isotypes can be utilized for distinct cellular functions during nervous system development. In the present review, we discuss: (i) the spectrum of congenital nervous system diseases that result from mutations in tubulin and MAPs (microtubule-associated proteins); (ii) the known or putative roles of these proteins during nervous system development; (iii) how the findings collectively support the ‘multi-tubulin’ hypothesis, which postulates that different tubulin isotypes may be required for specialized microtubule functions.