Putting 2 and 2 together

Wiedemann, Claudia

doi:10.1038/nrn2102

Research Highlight
Published: March 2007

Neuronal migration

Putting 2 and 2 together

Claudia Wiedemann

Nature Reviews Neuroscience volume 8, page 165 (2007)Cite this article

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α1 tubulin binds to β-tubulin, and the resulting heterodimers form the building blocks of microtubules. Microtubule formation is essential for neurite outgrowth and neuronal migration, which is required for the formation of laminar structures of certain brain regions, such as the cortex and the hippocampus. As part of a large-scale mutagenesis screen, Keays et al. tested more than 9000 mice carrying random mutations introduced by ethylnitrosourea (ENU) injections for mutations that cause behavioural abnormalities.

One mouse strain, called Jenna, was identified with a semi-dominant (Jen/⁺), hyperactive phenotype and the authors characterized these mice on the genetic, molecular, anatomical and behavioural level. They identified a point mutation in the GTP-binding pocket of α1 tubulin (TUBA1) which resulted in less efficient heterodimer formation with β-tubulin in in vitro studies; however, heterodimers could still polymerize to form microtubules.

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ORIGINAL RESEARCH PAPER

Keays, D. A. et al. Mutations in α-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128, 45–57 (2007)
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