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

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 represso...

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Published inDevelopment (Cambridge) Vol. 137; no. 11; pp. 1875 - 1885
Main Authors Shimizu, Takeshi, Nakazawa, Masato, Kani, Shuichi, Bae, Young-Ki, Shimizu, Takashi, Kageyama, Ryoichiro, Hibi, Masahiko
Format Journal Article
LanguageEnglish
Published England 01.06.2010
Subjects
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
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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.
AbstractList 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.
Author Shimizu, Takashi
Kageyama, Ryoichiro
Hibi, Masahiko
Nakazawa, Masato
Kani, Shuichi
Shimizu, Takeshi
Bae, Young-Ki
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/20431123$$D View this record in MEDLINE/PubMed
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Snippet Precise control of neuronal differentiation is necessary for generation of a variety of neurons in the forebrain. However, little is known about...
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SubjectTerms 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
Title Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain
URI https://www.ncbi.nlm.nih.gov/pubmed/20431123
https://search.proquest.com/docview/733124511
Volume 137
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