Prdm16 is Required for the Maintenance of Neural Stem Cells in the Postnatal Forebrain and Their Differentiation into Ependymal Cells

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2017 Jul 13

PMID 28698301

Citations 42

Authors

Issei S Shimada

Melih Acar

Rebecca J Burgess

Zhiyu Zhao

Sean J Morrison

Affiliations

Soon will be listed here.

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, 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 deletion during fetal development using Nestin-Cre prevented the formation of ependymal cells, disrupting cerebrospinal fluid flow and causing hydrocephalus. Postnatal deletion using -CreER 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.

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