Neural Differentiation Modulates the Vertebrate Brain Specific Splicing Program

Abstract : Alternative splicing patterns are known to vary between tissues but these patterns have been found to be predominantly peculiar to one species or another, implying only a limited function in fundamental neural biology. Here we used high-throughput RT-PCR to monitor the expression pattern of all the annotated simple alternative splicing events (ASEs) in the Reference Sequence Database, in different mouse tissues and identified 93 brain-specific events that shift from one isoform to another (switch-like) between brain and other tissues. Consistent with an important function, regulation of a core set of 9 conserved switch-like ASEs is highly conserved, as they have the same pattern of tissue-specific splicing in all vertebrates tested: human, mouse and zebrafish. Several of these ASEs are embedded within genes that encode proteins associated with the neuronal microtubule network, and show a dramatic and concerted shift within a short time window of human neural stem cell differentiation. Similarly these exons are dynamically regulated in zebrafish development. These data demonstrate that although alternative splicing patterns often vary between species , there is nonetheless a core set of vertebrate brain-specific ASEs that are conserved between species and associated with neural differentiation.
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Alicia Madgwick, Philippe Fort, Peter Hanson, Philippe Thibault, Marie-Claude Gaudreau, et al.. Neural Differentiation Modulates the Vertebrate Brain Specific Splicing Program. PLoS ONE, Public Library of Science, 2015, 10 (5), pp.e0125998. ⟨10.1371/journal.pone.0125998⟩. ⟨hal-02087009⟩



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