Format

Send to

Choose Destination
Genes Dev. 2017 Jun 1;31(11):1134-1146. doi: 10.1101/gad.291773.116. Epub 2017 Jul 11.

Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells.

Author information

1
Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
2
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
3
Bahcesehir University, School of Medicine, Istanbul 34734, Turkey.
4
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Abstract

We and others showed previously that PR domain-containing 16 (Prdm16) is a transcriptional regulator required for stem cell function in multiple fetal and neonatal tissues, including the nervous system. However, Prdm16 germline knockout mice died neonatally, preventing us from testing whether Prdm16 is also required for adult stem cell function. Here we demonstrate that Prdm16 is required for neural stem cell maintenance and neurogenesis in the adult lateral ventricle subventricular zone and dentate gyrus. We also discovered that Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle. Conditional Prdm16 deletion during fetal development using Nestin-Cre prevented the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing hydrocephalus. Postnatal Prdm16 deletion using Nestin-CreERT2 did not cause hydrocephalus or prevent the formation of ciliated ependymal cells but caused defects in their differentiation. Prdm16 was required in neural stem/progenitor cells for the expression of Foxj1, a transcription factor that promotes ependymal cell differentiation. These studies show that Prdm16 is required for adult neural stem cell maintenance and neurogenesis as well as the formation of ependymal cells.

KEYWORDS:

Prdm16; ependymal cell; hydrocephalus; neural stem cell

PMID:
28698301
PMCID:
PMC5538436
DOI:
10.1101/gad.291773.116
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center