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Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development

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Abstract

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.

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Acknowledgements

The authors thankfully acknowledge the financial assistance received from the Department of Biotechnology, New Delhi (BT/PR26189/GET/119/226/2017) and DST-SERB, New Delhi (EMR/2017/000465). Facilities extended by SRMIST are gratefully acknowledged. Tantry MSA is supported by the INSPIRE fellowship (DST/INSPIRE Fellowship/2019/IF190200) from the Department of Science and Technology, Government of India.

Funding

Department of Biotechnology, New Delhi (BT/PR26189/GET/119/226/2017); DST-SERB, New Delhi (EMR/2017/000465) and Department of Science and Technology, Government of India (DST/INSPIRE Fellowship/2019/IF190200).

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  1. Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, 603203, India

    M. S. Ananthakrishna Tantry & Kirankumar Santhakumar

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Both the authors contributed to the conceptualization and designing the manuscript. Mr. M S Ananthakrishna Tantry prepared the first draft of the manuscript, tables, figures, and curated the data. Dr. Santhakumar Kirankumar, as a principal investigator, critically revised the manuscript, and both the authors approved the version to be published.

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Tantry, M.S.A., Santhakumar, K. Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development. Mol Neurobiol 60, 3803–3823 (2023). https://doi.org/10.1007/s12035-023-03302-1

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