Tubulins are the highly conserved subunit of microtubules which involve in various fundamental functions including brain development. Microtubules help in neuronal proliferation, migration, differentiation, cargo transport along the axons, synapse formation, and many more.
Tubulin gene family consisting of multiple isotypes, their differential expression and varied post translational modifications create a whole new level of complexity and diversity in accomplishing manifold neuronal functions. The studies on the relation between
tubulin genes and brain development opened a new avenue to understand the role of each
tubulin isotype in neurodevelopment. Mutations in
tubulin genes are reported to cause brain development defects especially cortical malformations, referred as tubulinopathies. There is an increased need to understand the molecular correlation between various
tubulin mutations and the associated brain pathology. Recently, mutations in
tubulin isotypes (TUBA1A, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB3, and TUBG1) have been linked to cause various neurodevelopmental defects like
lissencephaly,
microcephaly,
cortical dysplasia,
polymicrogyria,
schizencephaly,
subcortical band heterotopia,
periventricular heterotopia,
corpus callosum agenesis, and cerebellar hypoplasia. This review summarizes on the microtubule dynamics, their role in neurodevelopment,
tubulin isotypes, post translational modifications, and the role of
tubulin mutations in causing specific neurodevelopmental defects. A comprehensive list containing all the reported
tubulin pathogenic variants associated with brain developmental defects has been prepared to give a bird's eye view on the broad range of
tubulin functions.