Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages.
Previous gene targeting studies in mice have implicated the nuclear protein Krüppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.
Caiazzo
Massimiliano
M
Institute of Genetics and Biophysics "A. Buzzati-Traverso," CNR, 80131 Naples, Italy. caiazzo@igb.cnr.it
Colucci-D'Amato
Luca
L
Esposito
Maria T
MT
Parisi
Silvia
S
Stifani
Stefano
S
Ramirez
Francesco
F
di Porzio
Umberto
U
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D054258:Neural Plate / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse