title: Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis.
abstract: Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of 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 to perform genome-wide m6A profiling and observed dynamic m6A modification during postnatal neurodevelopment. The loss of FTO led to the altered expression of several key components of the brain derived neurotrophic factor pathway that were marked by m6A. These results together suggest FTO plays important roles in neurogenesis, as well as in learning and memory.
authors.affiliation: Institute of Genetics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.|The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Genetics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.|The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zang
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Feiran
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Junchen
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.|School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
authors.forename: Liqi
authors.initials: L
authors.lastname: Shu
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
authors.forename: Huikang
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Tianlei
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: National Center for Protein Sciences Beijing, Life Sciences Park, Beijing 102206, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Tang
authors.affiliation: National Center for Protein Sciences Beijing, Life Sciences Park, Beijing 102206, China.
authors.forename: Pumin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shu
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.|The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D005786:Gene Expression Regulation; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO