Transient expression of Mnb/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling.

ABSTRACT: The decision of a neural precursor to stop dividing and begin its terminal differentiation at the correct place, and at the right time, is a crucial step in the generation of cell diversity in the nervous system. Here, we show that the Down's syndrome candidate gene (Mnb/Dyrk1a) is transiently expressed in prospective neurons of vertebrate CNS neuroepithelia. The gain of function (GoF) of Mnb/Dyrk1a induced proliferation arrest. Conversely, its loss of function (LoF) caused over proliferation and cell death. We found that MNB/DYRK1A is both necessary and sufficient to upregulate, at transcriptional level, the expression of the cyclin-dependent kinase inhibitor p27(KIP1) in the embryonic chick spinal cord and mouse telencephalon, supporting a regulatory role for MNB/DYRK1A in cell cycle exi

SUBMITTER: Hammerle B 

PROVIDER: S-EPMC3100710 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature