title: Axin directs the amplification and differentiation of intermediate progenitors in the developing cerebral cortex.
abstract: The expansion of the mammalian cerebral cortex is safeguarded by a concerted balance between amplification and neuronal differentiation of intermediate progenitors (IPs). Nonetheless, the molecular controls governing these processes remain unclear. We found that the scaffold protein Axin is a critical regulator that determines the IP population size and ultimately the number of neurons during neurogenesis in the developing cerebral cortex. The increase of the IP pool is mediated by the interaction between Axin and GSK-3 in the cytoplasmic compartments of the progenitors. Importantly, as development proceeds, Axin becomes enriched in the nucleus to trigger neuronal differentiation via β-catenin activation. The nuclear localization of Axin and hence the switch of IPs from proliferative to differentiative status are strictly controlled by the Cdk5-dependent phosphorylation of Axin at Thr485. Our results demonstrate an important Axin-dependent regulatory mechanism in neurogenesis, providing potential insights into the evolutionary expansion of the cerebral cortex.
authors: Division of Life Science, Molecular Neuroscience Center, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors: Wei-Qun
authors: WQ
authors: Fang
authors: Wei-Wei
authors: WW
authors: Chen
authors: Amy K Y
authors: AK
authors: Fu
authors: Nancy Y
authors: NY
authors: Ip
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D018274:Electroporation; D004622:Embryo, Mammalian; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D047468:Immunoprecipitation; D007276:Injections, Intraventricular; D051379:Mice; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D010766:Phosphorylation; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
chemical_list: D060466:Axin Protein; D034741:RNA, Small Interfering; D051176:beta Catenin; D013912:Threonine; D038362:Glycogen Synthase Kinase 3; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine