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Spatially dependent dynamic MAPK modulation by the Nde1-Lis1-Brap complex patterns mammalian CNS.

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 Cell

journal_title

Developmental cell

authors

Lanctot AA,Peng CY,Pawlisz AS,Joksimovic M,Feng Y

doi

10.1016/j.devcel.2013.04.006

subject

Has Abstract

pub_date

2013-05-13 00:00:00

pages

241-55

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(13)00217-7

journal_volume

25

pub_type

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