Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice

Song Qin, Menglu Liu, Wenze Niu, Chun Li Zhang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that downregulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.

Original languageEnglish (US)
Pages (from-to)21117-21121
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number52
DOIs
StatePublished - Dec 27 2011

Fingerprint

Hydrocephalus
Neural Stem Cells
Brain
Subcommissural Organ
Agenesis of Corpus Callosum
Cilia
Embryonic Stem Cells
Astrocytes
Hypertrophy
Transgenic Mice
Cerebrospinal Fluid
Stem Cells
Down-Regulation
Cell Proliferation
GKLF protein

Keywords

  • Ependymal cilia
  • Neurogenesis

ASJC Scopus subject areas

  • General

Cite this

Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice. / Qin, Song; Liu, Menglu; Niu, Wenze; Zhang, Chun Li.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 52, 27.12.2011, p. 21117-21121.

Research output: Contribution to journalArticle

@article{ccee810e6a184ba1a799e189bf07f59d,
title = "Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice",
abstract = "Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that downregulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.",
keywords = "Ependymal cilia, Neurogenesis",
author = "Song Qin and Menglu Liu and Wenze Niu and Zhang, {Chun Li}",
year = "2011",
month = "12",
day = "27",
doi = "10.1073/pnas.1112351109",
language = "English (US)",
volume = "108",
pages = "21117--21121",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "52",

}

TY - JOUR

T1 - Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice

AU - Qin, Song

AU - Liu, Menglu

AU - Niu, Wenze

AU - Zhang, Chun Li

PY - 2011/12/27

Y1 - 2011/12/27

N2 - Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that downregulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.

AB - Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that downregulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.

KW - Ependymal cilia

KW - Neurogenesis

UR - http://www.scopus.com/inward/record.url?scp=84862932899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862932899&partnerID=8YFLogxK

U2 - 10.1073/pnas.1112351109

DO - 10.1073/pnas.1112351109

M3 - Article

C2 - 22160720

AN - SCOPUS:84862932899

VL - 108

SP - 21117

EP - 21121

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 52

ER -