Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry (Nat Neurosci, 2009, 12:1020-1027)

報告日期: 2009/12/11
報告時間: 15:10/16:00
報告學生: 林宏國
講評老師: 許桂森
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/981211-1.pdf

Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry

Allison M Bond, Michael J W VanGompel, Evgeny A Sametsky, Mary F Clark, Julie C Savage, John F Disterhoft and Jhumku D Kohtz

Nature Neuroscience 12, 1020 - 1027 (2009)

 

Speaker: Hong-Guo Lin (林宏國)

Commentator: Kuei-Sen Hsu, Ph.D (許桂森 老師)

Date: 12/11 15:10 – 16:00

 

Abstract

Genomic studies demonstrate that, although the majority of the mammalian genome is transcribed, there are only about 2% of these transcripts coding for proteins. The previous study demonstrated that Evf2 noncoding RNA (ncRNA) is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. It is a novel mechanism whereby transcription is controlled by the cooperative actions of an ncRNA and a homeodomain protein. In present study, the authors further found that Evf2 recruited DLX and MECP2 transcriptional factors to important DNA regulatory elements in the Dlx5/6 and controlled Dlx5, Dlx6 and Gad1 expression through trans- and cis-acting mechanisms in developing ventral forebrain. In Evf2 mutant mice, there were reduced numbers of GABAergic interneurons in early postnatal hippocampus and dentate gyrus. Although the numbers of GABAergic interneurons and Gad1 RNA levels returned to normal in Evf2 mutant adult hippocampus, they found the synaptic inhibition did decrease. These results suggest that Evf2 noncoding RNA–dependent balanced gene regulation in embryonic brain is critical for proper formation of GABA-dependent neuronal circuitry in adult brain. Finally, for the best of their knowledge, the authors found for first time that the Evf2 ncRNA is important for gene regulation and the development of interneurons that produce GABA.

 

References

1.      Feng, J. et al. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev. 20, 1470–1484 (2006).

2.      Pleasure, S.J. et al. Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Neuron 28, 727–740 (2000).