RNAase-III enzyme Dicer maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells.
An important function of the RNAase-III enzyme Dicer is to process microRNA precursors into ~22-nucleotide non-coding small RNAs. But little is known about the role of Dicer in mammalian brain formation and neural stem cell (NSC) development. Here we show that Dicer plays a crucial role in controlling mouse cortical NSC development. We found that Dicer function is essential for expanding cortical neural progenitors and NSCs. We have identified a population of Dicer-deficient NSCs that can self-renew, and that display normal karyotype and heterochromatin protein expression levels but show enlarged nuclei. Dicer-deficient NSCs display abnormal differentiation and undergo cell death when mitogens are withdrawn. Dicer deletion affects the levels of many proteins, as revealed by a mass spectrometry proteomic approach. We have found that an increase of anti-survival and/or pro-apoptosis proteins and a decrease of pro-survival and/or anti-apoptosis proteins contribute to the cell death of Dicer-deficient NSCs, implying a general role for Dicer in protecting cells from apoptosis. Our results demonstrate important functions for Dicer in regulating NSC development by maintaining proper signaling pathways related to cell survival and differentiation.
Kawase-Koga
Yoko
Y
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, Box 60, New York, NY 10065, USA.
Low
Roger
R
Otaegi
Gaizka
G
Pollock
Andrew
A
Deng
Haiteng
H
Eisenhaber
Frank
F
Maurer-Stroh
Sebastian
S
Sun
Tao
T
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000201:enzymology*; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology*; D005260:Female; D006570:Heterochromatin / Q000378:metabolism; D007621:Karyotyping; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D011247:Pregnancy; D040081:Protein Array Analysis; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D017931:DNA Primers; D006570:Heterochromatin; D043244:Ribonuclease III