| First Author | Zhang J | Year | 2013 |
| Journal | Neural Dev | Volume | 8 |
| Pages | 7 | PubMed ID | 23618343 |
| Mgi Jnum | J:198573 | Mgi Id | MGI:5498415 |
| Doi | 10.1186/1749-8104-8-7 | Citation | Zhang J, et al. (2013) AKT activation by N-cadherin regulates beta-catenin signaling and neuronal differentiation during cortical development. Neural Dev 8:7 |
| abstractText | BACKGROUND: During cerebral cortical development, neural precursor-precursor interactions in the ventricular zone neurogenic niche coordinate signaling pathways that regulate proliferation and differentiation. Previous studies with shRNA knockdown approaches indicated that N-cadherin adhesion between cortical precursors regulates beta-catenin signaling, but the underlying mechanisms remained poorly understood. RESULTS: Here, with conditional knockout approaches, we find further supporting evidence that N-cadherin maintains beta-catenin signaling during cortical development. Using shRNA to N-cadherin and dominant negative N-cadherin overexpression in cell culture, we find that N-cadherin regulates Wnt-stimulated beta-catenin signaling in a cell-autonomous fashion. Knockdown or inhibition of N-cadherin with function-blocking antibodies leads to reduced activation of the Wnt co-receptor LRP6. We also find that N-cadherin regulates beta-catenin via AKT, as reduction of N-cadherin causes decreased AKT activation and reduced phosphorylation of AKT targets GSK3beta and beta-catenin. Inhibition of AKT signaling in neural precursors in vivo leads to reduced beta-catenin-dependent transcriptional activation, increased migration from the ventricular zone, premature neuronal differentiation, and increased apoptotic cell death. CONCLUSIONS: These results show that N-cadherin regulates beta-catenin signaling through both Wnt and AKT, and suggest a previously unrecognized role for AKT in neuronal differentiation and cell survival during cortical development. |
