Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.
Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs. Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function.
Neural Stem Cell Institute, Regenerative Research Foundation, Rensselaer, NY 12144, USA.
Gretchen
G
Kusek
Melissa
M
Campbell
Frank
F
Doyle
Scott A
SA
Tenenbaum
Michael
M
Kiebler
Sally
S
Temple
D000818:Animals; D060049:Asymmetric Cell Division; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000196:embryology* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C471845:stau2 protein, mouse; C514011:TRIM32 protein, mouse; D044767:Ubiquitin-Protein Ligases