Abstract:
: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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Lanctot AA,Peng CY,Pawlisz AS,Joksimovic M,Feng Ydoi
10.1016/j.devcel.2013.04.006subject
Has Abstractpub_date
2013-05-13 00:00:00pages
241-55issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(13)00217-7journal_volume
25pub_type
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