Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Letter Article

FoxF1 is Required for Ciliogenesis and Distribution of Sonic Hedgehog Signaling Components in Cilium

Author(s): Lu Huang, Marco Tjakra, Desha Luo, Lin Wen, Daoxi Lei, Jinxuan Wang, Tieying Yin, Xiaojuan Zhang, Junli Huang, Yeqi Wang* and Guixue Wang*

Volume 19, Issue 5, 2019

Page: [326 - 334] Pages: 9

DOI: 10.2174/1566524019666190405115420

Price: $65

Abstract

Background: In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation of ciliogenesis and in the distribution of Shh signaling components in cilium.

Methods: NIH/3T3 cells were serum starved for 24h to induce cilium. Meanwhile, shRNA was used to knockdown the FoxF1 expression in the cells and CRISPR/Cas9 was used to generate the FoxF1 zebrafish mutant. The mRNA and protein expression of indicated genes were detected by the qRT-PCR and western blot, respectively. Immunofluorescence staining was performed to detect the cilium and Shh components distribution.

Results: FoxF1 knockdown decreased the cilium length in NIH/3T3 cells. Meanwhile, the disruption of FoxF1 function inhibited the expression of cilium-related genes and caused an abnormal distribution of Shh components in the cilium. Furthermore, homozygous FoxF1 mutants exhibited defective development of pronephric cilium in early zebrafish embryos.

Conclusion: Together, our data illustrated that FoxF1 is required for ciliogenesis in vitro and in vivo and for the proper localization of Shh signaling components in cilium.

Keywords: FoxF1, cilium, ciliogenesis, Sonic Hedgehog, zebrafish mutants, pronephric cilium.

« Previous Next »
[1]
Satir P, Christensen ST. Overview of structure and function of mammalian cilia. Annu Rev Physiol 2007; 69: 377-400.
[2]
Ishikawa H, Marshall W. Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol 2011; 12: 222-34.
[3]
Gerdes JM, Davis EE, Katsanis N. The vertebrate primary cilium in development, homeostasis, and disease. Cell 2009; 137: 32-45.
[4]
Badano JL, Mitsuma N, Beales PL, et al. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 2006; 7: 125-48.
[5]
Tobin JL, Beales PL. The nonmotile ciliopathies. Genet Med 2009; 11: 386-402.
[6]
Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002; 3: 813-25.
[7]
Pedersen LB, Rosenbaum JL. Chapter Two Intraflagellar Transport (IFT). Role in ciliary assembly, resorption and signalling. Curr Top Dev Biol 2008; 85: 23-61.
[8]
Davenport JR, Watts AJ, Roper VC, et al. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr Biol 2007; 17: 1586-94.
[9]
Goetz SC, Anderson KV. The primary cilium: A signalling centre during vertebrate development. Nat Rev Genet 2010; 11: 331-44.
[10]
Huangfu D, Liu A, Rakeman AS, et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 2003; 426: 83-7.
[11]
Liem KF, He M, Ocbina PJR, et al. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc Natl Acad Sci 2009; 106: 13377-82.
[12]
Benayoun BA, Caburet S, Veitia RA. Forkhead transcription factors: key players in health and disease. Trends Genet 2011; 27: 224-32.
[13]
Mahlapuu M, Enerbäck S, Carlsson P. Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development 2001; 128: 2397-406.
[14]
Kalinichenko VV, Zhou Y, Bhattacharyya D, et al. Haploinsufficiency of the mouse forkhead box f1 gene causes defects in gall bladder development. J Biol Chem 2002; 277: 12369-74.
[15]
Ren X, Ustiyan V, Pradhan A, et al. FOXF1 transcription factor is required for formation of embryonic vasculature by regulating VEGF signaling in endothelial cells. Circ Res 2014; 115: 709-20.
[16]
Fleury M, Eliades A, Carlsson P, et al. FOXF1 inhibits hematopoietic lineage commitment during early mesoderm specification. Development 2015; 142: 3307-20.
[17]
Kalinichenko VV, Lim L, Clark J, et al. Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor. Dev Biol 2001; 235: 489-506.
[18]
Melboucy-Belkhir S, Pradère P, Tadbiri S, et al. Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro. Am J Physiol Cell Mol Physiol 2014; 307: L838-47.
[19]
Bohnenpoll T, Wittern AB, Mamo TM, et al. A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development. PLoS Genet 2017; 13: e1006951.
[20]
Westerfield M. The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). 5th Edition. Univ. Oregon Press 2007.
[21]
Montague TG, Cruz JM, Gagnon JA, et al. CHOPCHOP: A CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res 2014; 42: W401-7.
[22]
Gagnon JA, Valen E, Thyme SB, et al. Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 2014; 9: e98186.
[23]
Zhang K, Chen YD, Zhang T, et al. A novel role of id1 in regulating sscillatory shear stress-mediated lipid uptake in endothelial cells. Ann Biomed Eng 2018; 46: 849-63.
[24]
Thisse C, Thisse B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 2008; 3: 59-69.
[25]
Lo PK, Lee JS, Sukumar S. The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function. Cell Signal 2012; 24: 316-24.
[26]
He M, Subramanian R, Bangs F, et al. The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat Cell Biol 2014; 16: 663-72.
[27]
Song Z, Zhang X, Jia S, et al. Zebrafish as a model for human ciliopathies. J Genet Genomics 2016; 43: 107-20.
[28]
Lechtreck KF. IFT-Cargo interactions and protein transport in cilia. Trends Biochem Sci 2015; 40: 765-78.
[29]
Pazour GJ, Dickert BL, Vucica Y, et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene Tg737, are required for assembly of cilia and flagella. J Cell Biol 2000; 151: 709-18.
[30]
Liu A. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development 2005; 132: 3103-11.
[31]
Marszalek JR, Ruiz-Lozano P, Roberts E, et al. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc Natl Acad Sci USA 1999; 96: 5043-8.
[32]
Putoux A, Thomas S, Coene KLM, et al. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet 2011; 43: 601-6.
[33]
Wendling DS, Lück C, Von Schweinitz D, et al. Characteristic overexpression of the forkhead box transcription factor Foxf1 in Patched-associated tumors. Int J Mol Med 2008; 22: 787-92.
[34]
Millington G, Elliott KH, Chang YT, et al. Cilia-dependent GLI processing in neural crest cells is required for tongue development. Dev Biol 2017; 424: 124-37.
[35]
Haycraft CJ, Banizs B, Aydin-Son Y, et al. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 2005; 1: e53.
[36]
Huangfu D, Anderson KV. Cilia and hedgehog responsiveness in the mouse. Proc Natl Acad Sci 2005; 102: 11325-30.
[37]
K.M. Jaffe, S.Y. Thiberge, M.E. Bisher, R.D. Burdine. Imaging Cilia in Zebrafish 2010.
[http://dx.doi.org/10.1016/S0091- 679X(10)97022-2.]

Rights & Permissions Print Cite
Article Metrics
45
5
1
1
World Malaria Day
© 2024 Bentham Science Publishers | Privacy Policy