title: Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants.
abstract: ERK5 MAP kinase is highly expressed in the developing nervous system and has been implicated in promoting the survival of immature neurons in culture. However, its role in the development and function of the mammalian nervous system has not been established in vivo. Here, we report that conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB). Our data suggest that this is due to a decrease in proliferation and an increase in apoptosis in the subventricular zone and rostral migratory stream of ERK5 mutant mice. Interestingly, ERK5 mutant mice have smaller OB and are impaired in odor discrimination between structurally similar odorants. We conclude that ERK5 is a novel signaling pathway regulating developmental OB neurogenesis and olfactory behavior.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195-7234, USA.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zou
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Pan
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Wang
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Chang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Cathy
authors.initials: C
authors.lastname: Tournier
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
authors.forename: Zhengui
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D004195:Disease Models, Animal; D004585:Electrooculography / Q000379:methods; D004622:Embryo, Mammalian; D059330:GABAergic Neurons / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D020547:Lateral Ventricles / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D048054:Mitogen-Activated Protein Kinase 7 / Q000172:deficiency* / Q000235:genetics; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics; D009812:Odorants; D009830:Olfactory Bulb / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D010468:Perceptual Disorders / Q000235:genetics* / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D015398:Signal Transduction; D012903:Smell / Q000235:genetics
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D055748:SOXB1 Transcription Factors; D012794:Sialic Acids; C527783:Sox2 protein, mouse; C103469:polysialyl neural cell adhesion molecule; D048054:Mitogen-Activated Protein Kinase 7; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine