Dev Cell. 2019 May 20;49(4):632-642.e7. doi: 10.1016/j.devcel.2019.04.032. | PubMed

Rebecca E Andersen ¹ , Sung Jun Hong ¹ , Justin J Lim ² , Miao Cui ³ , Brock A Harpur ² , Elizabeth Hwang ⁴ , Ryan N Delgado ⁴ , Alexander D Ramos ⁴ , Siyuan John Liu ⁴ , Benjamin J Blencowe ² , Daniel A Lim ⁵

1. Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
2. Donnelly Centre and Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.
3. Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
4. Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
5. Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA. Electronic address: daniel.lim@ucsf.edu.

Abstract

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.

Presented by Rebecca Andersen