About this Research Topic

Background

Microtubules are highly dynamic polymers composed of heterodimers of alpha- and beta-tubulin proteins which are critical for various cellular functions including organelle positioning, intracellular trafficking, morphogenesis, and mitosis.
Microtubules are especially important in the brain, as they generate the necessary force required for neuronal migration, maturation, connectivity, and function. Reflecting these multiple specialized roles, a large number of alpha- and beta-tubulin genes, each encoding a different tubulin isotype, are expressed within the brain.
Mutations affecting tubulin isotypes give rise to a wide class of neurological disorders known as the “tubulinopathies”. While some tubulin mutations primarily cause neurodevelopmental defects such as cortical and subcortical malformations, other mutations in tubulins, tubulin-specific chaperones or microtubule-associated proteins primarily cause neurodegeneration.
How mutations in tubulins and related proteins can differentially affect the development or maintenance of neurons, causing either neurodevelopmental defects or neurodegeneration, is a major unresolved question of fundamental, diagnostic and clinical interest.

In the last decade or so, intensive efforts have been dedicated to identifying clinical hallmarks of tubulinopathies to improve their differential diagnosis. Neuroimaging has proved a valuable tool in the identification of neurodevelopmental tubulinopathies and functional studies have shed some light upon the pathogenesis of these disorders. Despite these advances, our knowledge about the molecular mechanisms underlying the etiology of these conditions remain fragmentary.
The goal of this Research Topic is to advance our knowledge of the molecular mechanisms governing microtubule functioning in neurons, the etiology of tubulinopathies and, at the same time, to describe the clinical characteristics linked to neurodevelopmental and neurodegenerative tubulinopathies with the objective to define possible clues for phenotype-genotype correlations.

We will consider original research articles, comprehensive reviews, and short communications in line with the Topic. More specifically, submissions may be related to (but not limited to) the following topics:
i) Functional studies aimed at understanding the precise molecular pathways affected by tubulin gene mutations
ii) Functional studies focused on mechanisms of microtubule regulation (e.g., molecular determinants of the tubulin code, role of microtubule-associated proteins) and how these might be perturbed by tubulin gene mutations
iii) Genetic and clinical studies that expand the phenotypical and mutational spectrum of tubulin-related disorders
iv) Identification of clinical hallmarks to further improve the differential diagnosis of tubulinopathies
v) Potential for novel therapeutic perspectives for the treatment of tubulinopathies.

Keywords: tubulin, microtubule, neurodevelopment, neurodegeneration, mutation, genotype, phenotype, Microtubule regulation, Therapeutic perspectives

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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