title: Reduced hippocampal neurogenesis and skill reaching performance in adult Emx1 mutant mice.
abstract: Mammalian homeobox gene Emx family is involved in the development of the rostral brain. Loss-of-function studies suggest that, despite the agenesis of corpus callosum, the Emx1 mutants display relatively modest defects compared to the Emx2 mutants. However, the role of the Emx1 in neurogenesis and brain function has never been explored. We used unbiased stereology to determine the number of proliferating progenitors and immature neurons in the adult neurogenic zones. Although previous studies have established that the formation of the dentate gyrus (DG) requires Emx2, we found that the adult Emx1 mutants also exhibited a smaller DG, reduced number of proliferating progenitor cells and immature neurons in the DG, in contrast to the indistinguishable level of neurogenesis in the subventricular zone when compared to the wild type mice. In view of the involvement of callosal projection neurons in mediating interhemispheric crosstalk and spatial coupling between the limbs, and the importance of DG in hippocampus-dependent function in learning and memory, we assessed motor and cognitive functions. Emx1 deletion impaired performance on a forelimb skill reaching task and attenuated training induced hippocampal neurogenesis, but it did not affect motor activity or basic motor function as evaluated in the open field, wire hanging and rotor rod tests. Unexpectedly, the adult Emx1 mutant mice did not exhibit impairment in spatial learning and memory in the Barnes maze test. Our data suggest that deletion of the Emx1 gene reduces hippocampal neurogenesis and affects higher motor function that requires extensive learning.
authors.affiliation: Department of Neurological Surgery (112C), University of California at San Francisco, UCSF and SFVAMC, 4150 Clement Street, San Francisco, CA 94121, USA, and Department of Neurosurgery, HuaShan Hospital, Shanghai, PR China.
authors.forename: Shwuhuey M
authors.initials: SM
authors.lastname: Hong
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Melanie
authors.initials: M
authors.lastname: Neumann
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.forename: Diana
authors.initials: D
authors.lastname: Lac
authors.forename: Xuanmin
authors.initials: X
authors.lastname: Lum
authors.forename: Philip R
authors.initials: PR
authors.lastname: Weinstein
authors.forename: Jialing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D019957:Motor Skills Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins