Published on July 1, 2017 in Hum Mol Genet volume 26(13).

PubMed ID: 28398475

DOI: 3111724

Abstract:

Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- andoxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity andintellectual disability. The role of FTO in neurodevelopment and neurogenesis,however, remains largely unknown. Here we show that FTO is expressed in adult neuralstem cells and neurons and displays dynamic expression during postnatalneurodevelopment. The loss of FTO leads to decreased brain size and body weight. Wefind that FTO deficiency could reduce the proliferation and neuronal differentiationof adult neural stem cells in vivo, which leads to impaired learning and memory.Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we went on toperform genome-wide m6A profiling and observed dynamic m6A modification duringpostnatal neurodevelopment. The loss of FTO led to the altered expression of severalkey components of the brain derived neurotrophic factor pathway that were marked bym6A. These results together suggest FTO plays important roles in neurogenesis, aswell as in learning and memory.CI - © The Author 2017. Published by Oxford University Press. All rights reserved. ForPermissions, please email: journals.permissions@oup.com.