Splicing Misdirects Migrants

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Science  30 Jul 2010:
Vol. 329, Issue 5991, pp. 493
DOI: 10.1126/science.329.5991.493-c

The mammalian brain develops from the inside out; neurons migrate radially outward as they mature. A gradient of the protein reelin helps to guide the establishment of the layers. Yano et al. found in mice that Nova2, a protein that regulates RNA splicing, affects the migration of cortical neurons by switching out exonic sequences in the mRNA encoding disabled-1 (Dab1), which is an important component of the reelin signaling pathway. Mice deficient in Nova2 showed reduced and disorganized cortical layers; these patterns resembled the cortical disruptions seen in mice carrying mutations in reelin signaling components. With Nova2 removed, the balance between the isoforms of Dab1 (with and without the exons) is perturbed, and inappropriate neuronal migration ensues.

Neuron 66, 848 (2010).

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