title: Zinc finger gene fez-like functions in the formation of subplate neurons and thalamocortical axons.
abstract: fez-like (fezl) is a forebrain-expressed zinc finger gene required for the formation of the hypothalamic dopaminergic and serotonergic (monoaminergic) neurons in zebrafish. To reveal its function in mammals, we analyzed the expression of the mouse orthologue of fezl and generated fezl-deficient mice by homologous recombination. Mouse fezl was expressed specifically in the forebrain from embryonic day 8.5. At mid-gestation, fezl expression was detected in subdomains of the forebrain, including the dorsal telencephalon and ventral diencephalon. Unlike the zebrafish fezl mutant too few, the fezl-deficient mice displayed normal development of hypothalamic monoaminergic neurons, but showed abnormal "hyperactive" behavior. In fezl(-/-) mice, the thalamocortical axons (TCA) were reduced in number and aberrantly projected to the cortex. These mutants had a reduced number of subplate neurons, which are involved in guiding the TCA from the dorsal thalamus, although the subplate neurons were born normally. These results suggest that fezl is required for differentiation or survival of the subplate neurons, and reduction of the subplate neurons in fezl-deficient mice leads to abnormal development of the TCA, providing a possible link between the transcriptional regulation of forebrain development and hyperactive behavior.
authors.affiliation: Department of Molecular Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tustomu
authors.initials: T
authors.lastname: Hirata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Suda
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Masahiro
authors.initials: M
authors.lastname: Narimatsu
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hibi
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011995:Recombination, Genetic; D013788:Thalamus / Q000196:embryology*; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D029961:Zebrafish Proteins; C418489:fezf2 protein, zebrafish