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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Dentate Gyrus / cytology
  • Ependymoglial Cells / cytology*
  • Forkhead Transcription Factors / genetics
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Lateral Ventricles / cytology
  • Lateral Ventricles / physiopathology
  • Mice
  • Neural Stem Cells / cytology
  • Neurogenesis / genetics*
  • Prosencephalon / cytology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • FOXJ1 protein, mouse
  • Forkhead Transcription Factors
  • Prdm16 protein, mouse
  • Transcription Factors