| First Author | Arimura N | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 36 | PubMed ID | 32917586 |
| Mgi Jnum | J:313612 | Mgi Id | MGI:6790749 |
| Doi | 10.1126/sciadv.aba1693 | Citation | Arimura N, et al. (2020) DSCAM regulates delamination of neurons in the developing midbrain. Sci Adv 6(36) |
| abstractText | For normal neurogenesis and circuit formation, delamination of differentiating neurons from the proliferative zone must be precisely controlled; however, the regulatory mechanisms underlying cell attachment are poorly understood. Here, we show that Down syndrome cell adhesion molecule (DSCAM) controls neuronal delamination by local suppression of the RapGEF2-Rap1-N-cadherin cascade at the apical endfeet in the dorsal midbrain. Dscam transcripts were expressed in differentiating neurons, and DSCAM protein accumulated at the distal part of the apical endfeet. Cre-loxP-based neuronal labeling revealed that Dscam knockdown impaired endfeet detachment from ventricles. DSCAM associated with RapGEF2 to inactivate Rap1, whose activity is required for membrane localization of N-cadherin. Correspondingly, Dscam knockdown increased N-cadherin localization and ventricular attachment area at the endfeet. Furthermore, excessive endfeet attachment by Dscam knockdown was restored by co-knockdown of RapGEF2 or N-cadherin Our findings shed light on the molecular mechanism that regulates a critical step in early neuronal development. |
