Details

Autor(en) / Beteiligte

• Fang, Wei-Qun
• Chen, Wei-Wei
• Fu, Amy K.Y.
• Ip, Nancy Y.

Titel

Axin Directs the Amplification and Differentiation of Intermediate Progenitors in the Developing Cerebral Cortex

Ist Teil von

• Neuron (Cambridge, Mass.), 2013-08, Vol.79 (4), p.665-679

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Axin increases the population of IPs and results in enhanced production of neurons•Cdk5-dependent phosphorylation of Axin promotes neurogenesis•Nucleocytoplasmic shuttling of Axin controls IP amplification and differentiation•Axin specifically interacts with GSK-3β or β-catenin to amplify or differentiate IPs Fang et al. discover a regulatory mechanism for neurogenesis involving the scaffold protein Axin. Subcellular localization of the scaffold protein Axin controls the balance between neural progenitor proliferation and differentiation and, ultimately, the number of neurons generated during neurogenesis.