title: Deletion of Numb/Numblike in glutamatergic neurons leads to anxiety-like behavior in mice.
abstract: Endocytic adaptor protein Numb is the first identified cell fate determinant in Drosophila melanogaster. It has been implicated in Notch signaling pathway and regulation of neural stem cells proliferation in the central nervous system. Numb is also expressed in postmitotic neurons, in vitro studies showed that Numb is involved in neuronal morphologic development, such as neurite growth, axonal growth and spine development. However, in vivo functions of Numb in the postmitotic neurons are largely unknown. Here we show that deletion of Numb/Numblike in glutamatergic neurons causes anxiety-like behavior in mouse. In this study, we conditionally deleted Numb and its homologous gene Numblike in the glutamatergic neurons in dorsal forebrain, and thoroughly characterized the behavioral phenotypes of mutant mice. On a battery of tests for anxiety-like behavior, the conditional double knockout mice showed increased anxiety-like behavior on light/dark exploration and novel open field tests, but not on elevated zero maze tests. The conditional double knockout mice also displayed novelty induced hyperactivity in novel open field test. Control measures of general health, motor functions, startle response, sensorimotor gating, depression-related behaviors did not show differences between genotypes. Our present findings provide new insight into the indispensable functions of Numb/Numblike in the brain and behavior, and suggest that Numb/Numblike may play a role in mediating neuronal functions that underlie behaviors related to anxiety.
authors.affiliation: West China Development and Stem Cell Institute, West China Second Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China.
authors.forename: Minyan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine & Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Li
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200123, China; Nerdbio Inc., SIP Biobay, Jiangsu 215213, China. Electronic address: huashunli@tongji.edu.cn.
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C106292:Numbl protein, mouse
keywords: Anxiety-like behavior; Behavioral screen; Conditional knockout; Endocytosis; Glutamatergic neurons; Numb