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Article

Cell Type-Specific Role of RNA Nuclease SMG6 in Neurogenesis

1
Leibniz Institute on Aging—Fritz Lipmann Institute (FLI), Beutenbergstr 11, 07745 Jena, Germany
2
Faculty of Biological Sciences, Friedrich-Schiller University of Jena, Beutenbergstr 11, 07745 Jena, Germany
3
State Key Laboratory of Microbial Technology, Shandong University, No. 72, Binhai Road, Qingdao 266237, China
*
Authors to whom correspondence should be addressed.
Present address: Deutsches Rheuma-Forschungszentrum (DRFZ), Virchowweg 12, 10117 Berlin, Germany.
Academic Editor: FengRu Tang
Cells 2021, 10(12), 3365; https://doi.org/10.3390/cells10123365
Received: 27 October 2021 / Revised: 22 November 2021 / Accepted: 26 November 2021 / Published: 30 November 2021
(This article belongs to the Special Issue Induced Impairment of Neurogenesis and Brain Diseases)
SMG6 is an endonuclease, which cleaves mRNAs during nonsense-mediated mRNA decay (NMD), thereby regulating gene expression and controling mRNA quality. SMG6 has been shown as a differentiation license factor of totipotent embryonic stem cells. To investigate whether it controls the differentiation of lineage-specific pluripotent progenitor cells, we inactivated Smg6 in murine embryonic neural stem cells. Nestin-Cre-mediated deletion of Smg6 in mouse neuroprogenitor cells (NPCs) caused perinatal lethality. Mutant mice brains showed normal structure at E14.5 but great reduction of the cortical NPCs and late-born cortical neurons during later stages of neurogenesis (i.e., E18.5). Smg6 inactivation led to dramatic cell death in ganglionic eminence (GE) and a reduction of interneurons at E14.5. Interestingly, neurosphere assays showed self-renewal defects specifically in interneuron progenitors but not in cortical NPCs. RT-qPCR analysis revealed that the interneuron differentiation regulators Dlx1 and Dlx2 were reduced after Smg6 deletion. Intriguingly, when Smg6 was deleted specifically in cortical and hippocampal progenitors, the mutant mice were viable and showed normal size and architecture of the cortex at E18.5. Thus, SMG6 regulates cell fate in a cell type-specific manner and is more important for neuroprogenitors originating from the GE than for progenitors from the cortex. View Full-Text
Keywords: SMG6; NMD; neurogenesis; neurodevelopmental syndromes SMG6; NMD; neurogenesis; neurodevelopmental syndromes
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MDPI and ACS Style

Guerra, G.M.; May, D.; Kroll, T.; Koch, P.; Groth, M.; Wang, Z.-Q.; Li, T.-L.; Grigaravičius, P. Cell Type-Specific Role of RNA Nuclease SMG6 in Neurogenesis. Cells 2021, 10, 3365. https://doi.org/10.3390/cells10123365

AMA Style

Guerra GM, May D, Kroll T, Koch P, Groth M, Wang Z-Q, Li T-L, Grigaravičius P. Cell Type-Specific Role of RNA Nuclease SMG6 in Neurogenesis. Cells. 2021; 10(12):3365. https://doi.org/10.3390/cells10123365

Chicago/Turabian Style

Guerra, Gabriela Maria, Doreen May, Torsten Kroll, Philipp Koch, Marco Groth, Zhao-Qi Wang, Tang-Liang Li, and Paulius Grigaravičius. 2021. "Cell Type-Specific Role of RNA Nuclease SMG6 in Neurogenesis" Cells 10, no. 12: 3365. https://doi.org/10.3390/cells10123365

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