MECP2 duplication and mutations impair NSCs differentiation via miR-197 regulated ADAM10
Posted 02 May 2018
bioRxiv DOI: 10.1101/312983
Posted 02 May 2018
How MECP2 (Methyl-CpG-binding protein 2) duplication affects cortex development remains elusive. We found that elevated MeCP2 expression promotes neurogenesis during cortex development in Tg(MECP2) mouse brain. Ectopic expression of MeCP2 in NPCs inhibits ADAM10 and hence compromises the NOTCH pathway during NPC differentiation. MeCP2 up-regulates miR-197 to down-regulate ADAM10. The enhanced NPC differentiation/migration in Tg(MECP2) embryonic brain can be repressed by overexpression of ADAM10 or a miR-197 inhibitor. Consistently, the reduced neurogenesis induced by three rare MECP2 missense mutations (H371R, E394K, G428S) identified in a Han Chinese autism spectrum disorders (ASD) cohort, can be reversed by miR-197 both in vitro and in vivo. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for neurogenesis, which is affected by both MeCP2 duplication and mutation.
- Downloaded 344 times
- Download rankings, all-time:
- Site-wide: 96,037
- In developmental biology: 2,585
- Year to date:
- Site-wide: 129,716
- Since beginning of last month:
- Site-wide: 97,158
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!