PMID- 15964824 OWN - NLM STAT- MEDLINE DCOM- 20050802 LR - 20181113 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 25 IP - 13 DP - 2005 Jul TI - Transcription factor KLF7 is important for neuronal morphogenesis in selected regions of the nervous system. PG - 5699-711 AB - The Kruppel-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 p21waf/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. FAU - Laub, Friedrich AU - Laub F AD - Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, and Department of Physiology and Biophysics at Weill Medical College of Cornell University, 535 East 70th St., New York, New York 10021, USA. FAU - Lei, Lei AU - Lei L FAU - Sumiyoshi, Hideaki AU - Sumiyoshi H FAU - Kajimura, Daisuke AU - Kajimura D FAU - Dragomir, Cecilia AU - Dragomir C FAU - Smaldone, Silvia AU - Smaldone S FAU - Puche, Adam C AU - Puche AC FAU - Petros, Timothy J AU - Petros TJ FAU - Mason, Carol AU - Mason C FAU - Parada, Luis F AU - Parada LF FAU - Ramirez, Francesco AU - Ramirez F LA - eng GR - AR38648/AR/NIAMS NIH HHS/United States GR - R01 AR038648/AR/NIAMS NIH HHS/United States GR - NS33199/NS/NINDS NIH HHS/United States GR - R37 AR038648/AR/NIAMS NIH HHS/United States GR - R37 NS033199/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Cdkn1a protein, mouse) RN - 0 (Cell Cycle Proteins) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (DNA-Binding Proteins) RN - 0 (Klf7 protein, mouse) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Axons/metabolism MH - Cell Cycle Proteins/genetics/metabolism MH - Cells, Cultured MH - Central Nervous System/*embryology/growth & development MH - Chromatin Immunoprecipitation MH - Cyclin-Dependent Kinase Inhibitor p21 MH - DNA-Binding Proteins/*genetics/*physiology MH - Embryo Loss/genetics MH - Gene Expression Regulation, Developmental MH - Immunoblotting MH - Immunohistochemistry MH - In Situ Hybridization MH - Kruppel-Like Transcription Factors MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - *Morphogenesis MH - Neurons/cytology/*metabolism MH - Olfactory Mucosa/cytology MH - Promoter Regions, Genetic MH - Retina/cytology MH - Tissue Distribution MH - Transcription Factors/*genetics/*physiology MH - Transcription, Genetic PMC - PMC1157008 EDAT- 2005/06/21 09:00 MHDA- 2005/08/03 09:00 PMCR- 2005/11/01 CRDT- 2005/06/21 09:00 PHST- 2005/06/21 09:00 [pubmed] PHST- 2005/08/03 09:00 [medline] PHST- 2005/06/21 09:00 [entrez] PHST- 2005/11/01 00:00 [pmc-release] AID - 25/13/5699 [pii] AID - 2485-04 [pii] AID - 10.1128/MCB.25.13.5699-5711.2005 [doi] PST - ppublish SO - Mol Cell Biol. 2005 Jul;25(13):5699-711. doi: 10.1128/MCB.25.13.5699-5711.2005.