title: Comparative analysis of developmentally regulated expressions of Gadd45a, Gadd45b, and Gadd45g in the mouse and marmoset cerebral cortex.
abstract: The cerebral cortex is an indispensable region that is involved in higher cognitive function in the mammalian brain, and is particularly evolved in the primate brain. It has been demonstrated that cortical areas are formed by both innate and activity-dependent mechanisms. However, it remains unknown what molecular changes induce cortical expansion and complexity during primate evolution. Active DNA methylation/demethylation is one of the epigenetic mechanisms that can modify gene expression via the methylation/demethylation of promoter regions. Three growth arrest and DNA damage-inducible small nuclear proteins, Gadd45 alpha, beta, and gamma, have been identified as regulators of methylation status. To understand the involvement of epigenetic factors in primate cortical evolution, we started by analyzing expression of these demethylation genes in the developing common marmoset (Callithrix jacchus) and mouse (Mus musculus) brain. In the marmoset brain, we found that cortical expression levels of Gadd45 alpha and gamma were reduced during development, whereas there was high expression of Gadd45 beta in some areas of the adult brain, including the prefrontal, temporal, posterior parietal and insula cortices, which are particularly expanded in greater primates and humans. Compared to the marmoset brain, there were no clear regional differences and constant or reduced Gadd45 expression was seen between juvenile and adult mouse brain. Double staining with a neuronal marker revealed that most Gadd45-expressing cells were NeuN-positive neurons. Thus, these results suggest the possibility that differential Gadd45 expression affects neurons, contributing cortical evolution and diversity.
authors.affiliation: Laboratory for Symbolic Cognitive Development, RIKEN Brain Science Institute, Hirosawa 2-1, Wako 351-0198, Japan. Electronic address: Eiji.Matsunaga@brain.riken.jp.
authors.forename: E
authors.initials: E
authors.lastname: Matsunaga
authors.affiliation: Laboratory for Symbolic Cognitive Development, RIKEN Brain Science Institute, Hirosawa 2-1, Wako 351-0198, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nambu
authors.affiliation: Laboratory for Symbolic Cognitive Development, RIKEN Brain Science Institute, Hirosawa 2-1, Wako 351-0198, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.affiliation: Laboratory for Symbolic Cognitive Development, RIKEN Brain Science Institute, Hirosawa 2-1, Wako 351-0198, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Iriki
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002144:Callithrix / Q000254:growth & development* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice / Q000254:growth & development* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D013045:Species Specificity; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000097642:GADD45 Proteins; C499072:Gadd45a protein, mouse; C490125:Gadd45b protein, mouse; C121373:Gadd45g protein, mouse; C492380:NeuN protein, mouse; C092069:activity regulated cytoskeletal-associated protein
keywords: Gadd45; cerebral cortex; development; epigenetic; marmoset; mouse