Roles of intron retention and splicing factors in axons

In recent years, RNA dynamics in axons and dendrites have arisen as central to neuronal maturation and maintenance of healthy neuronal connectivity. However, the functional roles of transported mRNAs and their binding proteins are scarcely understood. Some of the proteins associated to local mRNAs are splicing factors and spliceosome proteins. We recently demonstrated that their axonal role is complex, as, in developing neurons in vivo, the splicing factor SFPQ and the U1 spliceosome protein snRNP70 locally control axonal shape and connectivity, through modulation of the local transcriptome. These findings open two essential questions: how are these splicing proteins shaping the transcriptome landscape locally and what is the molecular nature of the axonal interactions between specific mRNAs and these two proteins? Moreover, the recent findings of axonal and dendritic partially spliced mRNAs, retaining a single intron, open the additional question of the role(s) of intron-retaining transcripts in neurites and the possibility of direct functional interaction between retained introns and splicing proteins. We propose to answer these essential questions, at cellular and molecular levels, using zebrafish developing neurons (in embryos and in culture) as experimental models.