| First Author | Lanctot AA | Year | 2013 |
| Journal | Dev Cell | Volume | 25 |
| Issue | 3 | Pages | 241-55 |
| PubMed ID | 23673330 | Mgi Jnum | J:197131 |
| Mgi Id | MGI:5490918 | Doi | 10.1016/j.devcel.2013.04.006 |
| Citation | Lanctot AA, et al. (2013) Spatially dependent dynamic MAPK modulation by the nde1-lis1-brap complex patterns Mammalian CNS. Dev Cell 25(3):241-55 |
| abstractText | Regulating cell proliferation and differentiation in CNS development requires both extraordinary complexity and precision. Neural progenitors receive graded overlapping signals from midline signaling centers, yet each makes a unique cell fate decision in a spatiotemporally restricted pattern. The Nde1-Lis1 complex regulates individualized cell fate decisions based on the geographical location with respect to the midline. While cells distant from the midline fail to self-renew in the Nde1-Lis1 double-mutant CNS, cells embedded in the signaling centers showed marked overproliferation. A direct interaction between Lis1 and Brap, a mitogen-activated protein kinase (MAPK) signaling threshold modulator, mediates this differential response to mitogenic signal gradients. Nde1-Lis1 deficiency resulted in a spatially dependent alteration of MAPK scaffold Ksr and hyperactivation of MAPK. Epistasis analyses supported synergistic Brap and Lis1 functions. These results suggest that a molecular complex composed of Nde1, Lis1, and Brap regulates the dynamic MAPK signaling threshold in a spatially dependent fashion. |
