Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain

Takeshi Shimizu; Masato Nakazawa; Shuichi Kani; Young-Ki Bae; Takashi Shimizu; Ryoichiro Kageyama; Masahiko Hibi

doi:10.1242/dev.047167

Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain

Development. 2010 Jun;137(11):1875-85. doi: 10.1242/dev.047167. Epub 2010 Apr 28.

Authors

Takeshi Shimizu¹, Masato Nakazawa, Shuichi Kani, Young-Ki Bae, Takashi Shimizu, Ryoichiro Kageyama, Masahiko Hibi

Affiliation

¹ Laboratory for Vertebrate Axis Formation, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.

PMID: 20431123
DOI: 10.1242/dev.047167

Abstract

Precise control of neuronal differentiation is necessary for generation of a variety of neurons in the forebrain. However, little is known about transcriptional cascades, which initiate forebrain neurogenesis. Here we show that zinc finger genes Fezf1 and Fezf2, which encode transcriptional repressors, are expressed in the early neural stem (progenitor) cells and control neurogenesis in mouse dorsal telencephalon. Fezf1- and Fezf2-deficient forebrains display upregulation of Hes5 and downregulation of neurogenin 2, which is known to be negatively regulated by Hes5. We show that FEZF1 and FEZF2 bind to and directly repress the promoter activity of Hes5. In Fezf1- and Fezf2-deficient telencephalon, the differentiation of neural stem cells into early-born cortical neurons and intermediate progenitors is impaired. Loss of Hes5 suppresses neurogenesis defects in Fezf1- and Fezf2-deficient telencephalon. Our findings reveal that Fezf1 and Fezf2 control differentiation of neural stem cells by repressing Hes5 and, in turn, by derepressing neurogenin 2 in the forebrain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / deficiency
Basic Helix-Loop-Helix Transcription Factors / genetics*
Cell Differentiation / genetics
Cell Differentiation / physiology
Cell Line
DNA Primers / genetics
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics*
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism
Female
Gene Expression Regulation, Developmental
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / genetics*
Neurogenesis / genetics
Neurogenesis / physiology
Neurons / cytology
Neurons / metabolism*
Pregnancy
Promoter Regions, Genetic
Prosencephalon / embryology*
Prosencephalon / metabolism*
Recombinant Proteins / genetics
Repressor Proteins / deficiency
Repressor Proteins / genetics*
Telencephalon / embryology
Telencephalon / metabolism
Zinc Fingers / genetics

Substances

Basic Helix-Loop-Helix Transcription Factors
DNA Primers
DNA-Binding Proteins
Hes5 protein, mouse
Nerve Tissue Proteins
Neurog2 protein, mouse
Recombinant Proteins
Repressor Proteins
Zfp312 protein, mouse