| First Author | Cornell B | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 20 | Pages | 4405-4418 |
| PubMed ID | 28173130 | Mgi Jnum | J:273137 |
| Mgi Id | MGI:6283902 | Doi | 10.1093/hmg/ddw270 |
| Citation | Cornell B, et al. (2016) Regulation of neuronal morphogenesis by 14-3-3epsilon (Ywhae) via the microtubule binding protein, doublecortin. Hum Mol Genet 25(20):4405-4418 |
| abstractText | 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 14-3-3epsilon. Furthermore, duplication of this minimum region is strongly associated with the appearance of ASD in human patients, thus implicating the overexpression of 14-3-3epsilon in ASD. Using in vitro and in vivo techniques, we have found that 14-3-3epsilon binds to the microtubule binding protein doublecortin preventing its degradation. We also found that 14-3-3epsilon 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 14-3-3epsilon in neurite formation, we used 14-3-3epsilon flox mice and found that 14-3-3epsilon deficiency results in an increase in neurite formation. Our findings provide the first evidence of cellular pathology in 17p13.3 microduplication syndrome. |
