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Seminars

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[Seminar Notification] : Ki Jun Yoon, Ph.D. (05.09.2019)
2019-05-03

1. Title: Deciphering the neural epitranscriptome using mouse and human brain organoid models 

2. Speaker:  Ki Jun Yoon, Ph.D.
3. Affiliation: Department of Biological Sciences, KAIST ,Korea
4. Date: 2019. 05.09. (Thu) 16:00
5. Place: SIMS Main Building, Auditorium 109(1F)
6. Abstract:

Proper development of the nervous system is critical for its function, and deficits in neural development have been implicated in many brain disorders. A precise and predictable developmental schedule requires highly coordinated transcriptional cascades that orchestrate the dynamics of mammalian cortical neurogenesis. Recent discoveries of widespread mRNA chemical modifications raise the question of whether this mechanism plays post-transcriptional regulatory role in cortical neurogenesis. N6-methyladenosine (m6A), installed by the Mettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNA modification. However, the function of m6A methylation in mammalian brain development is largely unknown. Here we used the Mettl14 conditional knockout mouse as a model to examine m6A function in embryonic cortical neurogenesis in vivo. Mettl14 deletion in the embryonic mouse brain resulted in diminished m6A content, altered cell cycle progression of radial glial cells, and impaired temporal progression of the cortical development. To gain insight into the potential molecular mechanism underlying m6A dependent regulation, we performed m6A-seq from mouse developing forebrain and identified high confident m6A peaks on gene transcripts related to transcription factors, cell cycle and neuron differentiation. In addition, using m6A-seq datasets from mouse forebrain and human forebrain organoids, we revealed conserved and unique m6A mRNA methylation landscapes of mouse and human cortical neurogenesis. Together, our results reveal critical epitranscriptomic control of mammalian cortical neurogenesis and novel insight into mechanisms underlying this highly coordinated developmental program.