The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo

被引：52

作者：

Andersen, Rebecca E. ^{[1
,2
,3
]}

Hong, Sung Jun ^{[1
,2
,3
]}

Lim, Justin J. ^{[6
,7
]}

Cui, Miao ^{[1
,2
]}

Harpur, Brock A. ^{[6
,7
]}

Hwang, Elizabeth ^{[1
,2
,4
]}

Delgado, Ryan N. ^{[1
,2
,4
]}

Ramos, Alexander D. ^{[1
,2
,4
]}

Liu, Siyuan John ^{[1
,2
,4
]}

Blencowe, Benjamin J. ^{[6
,7
]}

Lim, Daniel A. ^{[1
,2
,5
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Eli & Edythe Brd Ctr Regenerat Med & Stem Cell Re, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dev & Stem Cell Biol Grad Program, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Biomed Sci Grad Program, Med Scientist Training Program, San Francisco, CA 94143 USA

[5] San Francisco VA Med Ctr, San Francisco, CA 94121 USA

[6] Univ Toronto, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada

[7] Univ Toronto, Dept Mol Genet, 160 Coll St, Toronto, ON M5S 3E1, Canada

来源：

DEVELOPMENTAL CELL | 2019年 / 49卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NEURAL STEM-CELLS; NEURONAL DIFFERENTIATION; TRANSCRIPTION; EXPRESSION; SPECIFICATION; CHROMATIN; DOMAINS;

D O I：

10.1016/j.devcel.2019.04.032

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

While it is now appreciated that certain long noncoding RNAs (lncRNAs) have important functions in cell biology, relatively few have been shown to regulate development in vivo, particularly with genetic strategies that establish cis versus trans mechanisms. Pnky is a nuclear-enriched lncRNA that is transcribed divergently from the neighboring proneural transcription factor Pou3f2. Here, we show that conditional deletion of Pnky from the developing cortex regulates the production of projection neurons from neural stem cells (NSCs) in a cell-autonomous manner, altering postnatal cortical lamination. Surprisingly, Pou3f2 expression is not disrupted by deletion of the entire Pnky gene. Moreover, expression of Pnky from a BAC transgene rescues the differential gene expression and increased neurogenesis of Pnky-knockout NSCs, as well as the developmental phenotypes of Pnky-deletion in vivo. Thus, despite being transcribed divergently from a key developmental transcription factor, the lncRNA Pnky regulates development in trans.

引用

页码：632 / +

页数：18

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