[대학원 생명과학과 세미나 안내]
연사 : 윤기준 교수 (KAIST 생명과학과)
연제 : Deciphering neural epitranscriptome
일시 : 2019년 5월 24일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 김윤기 교수
Abstract
Proper development of thenervous system is critical for its function, and deficits in neural developmenthave been implicated in many brain disorders. A precise and predictabledevelopmental schedule requires highly coordinated transcriptional cascadesthat orchestrate the dynamics of mammalian cortical neurogenesis. Recentdiscoveries of widespread mRNA chemical modifications raise the question of whetherthis mechanism plays post-transcriptional regulatory role in corticalneurogenesis. N6-methyladenosine (m6A), installed by theMettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNAmodification. However, thefunction of m6A methylation in mammalian brain development is largelyunknown. Here we used the Mettl14conditional knockout mouse as a model to examine m6A function inembryonic cortical neurogenesis in vivo. Mettl14 deletion in the embryonic mouse brain resultedin diminished m6A content, altered cell cycle progression of radialglial cells, and impaired temporal progression of the cortical development. To gain insight into the potentialmolecular mechanism underlying m6A dependent regulation, we performedm6A-seq from mouse developing forebrain and identified highconfident m6A peaks on gene transcripts relatedto transcription factors, cell cycle and neuron differentiation. In addition, using m6A-seqdatasets from mouse forebrain and human forebrain organoids, we revealedconserved and unique m6A mRNA methylation landscapes of mouse andhuman cortical neurogenesis.Together, our results reveal critical epitranscriptomic control of mammaliancortical neurogenesis and novel insight into mechanisms underlying this highlycoordinated developmental program.