Regulation of neuronal morphogenesis by 14-3-3epsilon (Ywhae) via the microtubule binding protein, doublecortin (vol 25, pg 4405, 2016)

17p13.3 microduplication syndrome is a newly identified genetic disorder characterized by duplications in the 17p13.3 chromosome locus, resulting in a variety of disorders including autism spectrum disorder (ASD). Importantly, a minimum duplication region has been defined, and this region exclusively contains the gene encoding 14-3-3 epsilon. Furthermore, duplication of this minimum region is strongly associated with the appearance of ASD in human patients, thus implicating lthe overexpression of 14-3-3 epsilon in ASD. Using in vitro and in vivo techniques, we have found that 14-3-3 epsilon binds to the microtubule binding protein doublecortin preventing its degradation. We also found that 14-3-3 epsilon overexpression disrupts neurite formation by preventing the invasion of microtubules into primitive neurites, which can be rescued by the knockdown of doublecortin. To analyse the function of 14-3-3 epsilon in neurite formation, we used 14-3-3 epsilon flox mice and found that 14-3-3 epsilon deficiency results in an increase in neurite formation. Our findings provide the first evidence of cellular pathology in 17p13.3 microduplication syndrome.