Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system

Friedrich Laub, Lei Lei, Hideaki Sumiyoshi, Daisuke Kajimura, Cecilia Dragomir, Silvia Smaldone, Adam C. Puche, Timothy J. Petros, Carol Mason, Luis F. Parada, Francesco Ramirez

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The Krüppel-like transcription factors (KLFs) are important regulators of cell proliferation and differentiation in several different organ systems. The mouse Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous system, and the corresponding protein stimulates transcription of the cyclin-dependent kinase inhibitor p21waf/cip gene. Here we report that loss of KLF7 activity in mice leads to neonatal lethality and a complex phenotype which is associated with deficits in neurite outgrowth and axonal misprojection at selected anatomical locations of the nervous system. Affected axon pathways include those of the olfactory and visual systems, the cerebral cortex, and the hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7 activity in the olfactory epithelium with significant downregulation of the p21waf/cip and p27kip1 genes. Cotransfection experiments extended the last finding by documenting KLF7's ability to transactivate a reporter gene construct driven by the proximal promoter of p27kip1. Consistent with emerging evidence for a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented p21 waf/cip and p27kip1 accumulation in the cytoplasm of differentiating olfactory sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth.

Original languageEnglish (US)
Pages (from-to)5699-5711
Number of pages13
JournalMolecular and Cellular Biology
Volume25
Issue number13
DOIs
StatePublished - Jul 2005

Fingerprint

Morphogenesis
Nervous System
Transcription Factors
Olfactory Receptor Neurons
Genes
Olfactory Mucosa
Cytoskeletal Proteins
Cyclin-Dependent Kinases
Reporter Genes
Cerebral Cortex
In Situ Hybridization
Axons
Cell Differentiation
Hippocampus
Cytoplasm
Down-Regulation
Cell Proliferation
Phenotype
Proteins
Neuronal Outgrowth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. / Laub, Friedrich; Lei, Lei; Sumiyoshi, Hideaki; Kajimura, Daisuke; Dragomir, Cecilia; Smaldone, Silvia; Puche, Adam C.; Petros, Timothy J.; Mason, Carol; Parada, Luis F.; Ramirez, Francesco.

In: Molecular and Cellular Biology, Vol. 25, No. 13, 07.2005, p. 5699-5711.

Research output: Contribution to journalArticle

Laub, F, Lei, L, Sumiyoshi, H, Kajimura, D, Dragomir, C, Smaldone, S, Puche, AC, Petros, TJ, Mason, C, Parada, LF & Ramirez, F 2005, 'Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system', Molecular and Cellular Biology, vol. 25, no. 13, pp. 5699-5711. https://doi.org/10.1128/MCB.25.13.5699-5711.2005
Laub, Friedrich ; Lei, Lei ; Sumiyoshi, Hideaki ; Kajimura, Daisuke ; Dragomir, Cecilia ; Smaldone, Silvia ; Puche, Adam C. ; Petros, Timothy J. ; Mason, Carol ; Parada, Luis F. ; Ramirez, Francesco. / Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 13. pp. 5699-5711.
@article{4691bba952f64ddc8ab543ff25e50ba5,
title = "Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system",
abstract = "The Kr{\"u}ppel-like transcription factors (KLFs) are important regulators of cell proliferation and differentiation in several different organ systems. The mouse Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous system, and the corresponding protein stimulates transcription of the cyclin-dependent kinase inhibitor p21waf/cip gene. Here we report that loss of KLF7 activity in mice leads to neonatal lethality and a complex phenotype which is associated with deficits in neurite outgrowth and axonal misprojection at selected anatomical locations of the nervous system. Affected axon pathways include those of the olfactory and visual systems, the cerebral cortex, and the hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7 activity in the olfactory epithelium with significant downregulation of the p21waf/cip and p27kip1 genes. Cotransfection experiments extended the last finding by documenting KLF7's ability to transactivate a reporter gene construct driven by the proximal promoter of p27kip1. Consistent with emerging evidence for a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented p21 waf/cip and p27kip1 accumulation in the cytoplasm of differentiating olfactory sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth.",
author = "Friedrich Laub and Lei Lei and Hideaki Sumiyoshi and Daisuke Kajimura and Cecilia Dragomir and Silvia Smaldone and Puche, {Adam C.} and Petros, {Timothy J.} and Carol Mason and Parada, {Luis F.} and Francesco Ramirez",
year = "2005",
month = "7",
doi = "10.1128/MCB.25.13.5699-5711.2005",
language = "English (US)",
volume = "25",
pages = "5699--5711",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "13",

}

TY - JOUR

T1 - Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system

AU - Laub, Friedrich

AU - Lei, Lei

AU - Sumiyoshi, Hideaki

AU - Kajimura, Daisuke

AU - Dragomir, Cecilia

AU - Smaldone, Silvia

AU - Puche, Adam C.

AU - Petros, Timothy J.

AU - Mason, Carol

AU - Parada, Luis F.

AU - Ramirez, Francesco

PY - 2005/7

Y1 - 2005/7

N2 - The Krüppel-like transcription factors (KLFs) are important regulators of cell proliferation and differentiation in several different organ systems. The mouse Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous system, and the corresponding protein stimulates transcription of the cyclin-dependent kinase inhibitor p21waf/cip gene. Here we report that loss of KLF7 activity in mice leads to neonatal lethality and a complex phenotype which is associated with deficits in neurite outgrowth and axonal misprojection at selected anatomical locations of the nervous system. Affected axon pathways include those of the olfactory and visual systems, the cerebral cortex, and the hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7 activity in the olfactory epithelium with significant downregulation of the p21waf/cip and p27kip1 genes. Cotransfection experiments extended the last finding by documenting KLF7's ability to transactivate a reporter gene construct driven by the proximal promoter of p27kip1. Consistent with emerging evidence for a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented p21 waf/cip and p27kip1 accumulation in the cytoplasm of differentiating olfactory sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth.

AB - The Krüppel-like transcription factors (KLFs) are important regulators of cell proliferation and differentiation in several different organ systems. The mouse Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous system, and the corresponding protein stimulates transcription of the cyclin-dependent kinase inhibitor p21waf/cip gene. Here we report that loss of KLF7 activity in mice leads to neonatal lethality and a complex phenotype which is associated with deficits in neurite outgrowth and axonal misprojection at selected anatomical locations of the nervous system. Affected axon pathways include those of the olfactory and visual systems, the cerebral cortex, and the hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7 activity in the olfactory epithelium with significant downregulation of the p21waf/cip and p27kip1 genes. Cotransfection experiments extended the last finding by documenting KLF7's ability to transactivate a reporter gene construct driven by the proximal promoter of p27kip1. Consistent with emerging evidence for a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented p21 waf/cip and p27kip1 accumulation in the cytoplasm of differentiating olfactory sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in part by optimizing the levels of molecules that promote axon outgrowth.

UR - http://www.scopus.com/inward/record.url?scp=20744439366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20744439366&partnerID=8YFLogxK

U2 - 10.1128/MCB.25.13.5699-5711.2005

DO - 10.1128/MCB.25.13.5699-5711.2005

M3 - Article

VL - 25

SP - 5699

EP - 5711

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 13

ER -