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

87 Scopus citations

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 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Laub, F., Lei, L., Sumiyoshi, H., Kajimura, D., Dragomir, C., Smaldone, S., Puche, A. C., Petros, T. J., Mason, C., Parada, L. F., & Ramirez, F. (2005). Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. Molecular and cellular biology, 25(13), 5699-5711. https://doi.org/10.1128/MCB.25.13.5699-5711.2005