Murine pluripotent stem cells with a homozygous knockout of Foxg1 show reduced differentiation towards cortical progenitors in vitro

Stem Cell Research
Eva Maria MallHeiner Niemann

Abstract

Foxg1 is a transcription factor critical for the development of the mammalian telencephalon. Foxg1 controls the proliferation of dorsal telencephalon progenitors and the specification of the ventral telencephalon. Homozygous knockout of Foxg1 in mice leads to severe microcephaly, attributed to premature differentiation of telencephalic progenitors, mainly of cortical progenitors. Here, we analyzed the influence of a Foxg1 knockout on differentiation of murine pluripotent stem cells (mPSCs) in an in vitro model of neuronal development. Murine PSCs were prone to neuronal differentiation in embryoid body like culture with minimal medium conditions, based on the intrinsic default of PSCs to develop into cortical progenitors. Differences between Foxg1 wildtype (Foxg1WT) and knockout (Foxg1KO) mPSCs were analyzed. Several mPSC lines with homozygous mutations in Foxg1 were produced using the CRISPR/Cas9 system leading to loss of functional domains. Analysis of mRNA expression using quantitative Real-Time (q) PCR revealed that Foxg1KO mPSCs expressed significantly less mRNA of Foxg1, Emx1, and VGlut1 compared to Foxg1WT controls, indicating reduced differentiation towards dorsal telencephalic progenitors. However, the size of the deriv...Continue Reading

Citations

Dec 12, 2019·Frontiers in Pediatrics·Nuwan C Hettige, Carl Ernst
May 21, 2020·Cellular Reprogramming·Monika Nowak-ImialekHeiner Niemann

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