Abstract
The forkhead box subclass O (FoxO) family of proteins is a group of highly evolutionary conserved transcription factors that regulate various cellular processes and embryonic development. Dysregulated expressions of FOXO genes have been identified in numerous tumors and genetic disorders. The expression of FOXO/Foxo, particularly FOXO4/Foxo4 and FOXO6/Foxo6, in the developing nervous system has not been fully characterized. Here, we identified zebrafish foxo4, foxo6a, and foxo6b homologs and demonstrated that all three genes were expressed in the developing nervous system. foxo4, foxo6a, and foxo6b displayed ubiquitous expression in the brain and later in distinct brain tissues. In addition, these three genes were expressed in different retinal layers in a time-dependent manner. Furthermore, the mRNA expression of all three genes was significantly downregulated after treatment with a selective PI3-kinase (PI3K) inhibitor, LY294002. Our results suggest that foxo4, foxo6a, and foxo6b play important roles in the developing brain and retina and that the transcriptional levels of these genes are regulated by PI3-kinase signaling.
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Acknowledgements
We thank the Taiwan Zebrafish Core facility at ZeTH and the Zebrafish Core in Academia Sinica for providing the experimental fish. This work was supported by grants from the Chang Gung Medical Foundation and Chang Gung Memorial Hospital (CMRPD1E0111, CMRPF1F016, and BMRP857) and the Ministry of Science and Technology of Taiwan (102-2311-B-182-002-MY3) for SJL, HYS and YCC, and the Chang Gung Memorial Hospital (CMRPG2F0241 and CMRPG2F02410251) for KCC.
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Communicated by Caroline Brennan
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Fig. S1
Temporal expression of zebrafish foxo4, foxo6a, and foxo6b by RT-PCR. RT-PCR analysis showing that zebrafish foxo4, foxo6a, and foxo6b transcripts were detected from 5 hpf to 96 hpf stages. foxo4 displayed relatively weak expression at 10 hpf and a high level between 24 and 72 hpf, whereas foxo6a and foxo6b expression were detected at low levels from 5 hpf but reached high levels between 24 and 72 hpf. Bottom bands show ef1α as a loading control. bp, base pair; hpf, hours post fertilization; M, DNA marker; NC, negative control. (GIF 31 kb)
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Lin, SJ., Chiang, MC., Shih, HY. et al. Spatiotemporal expression of foxo4, foxo6a, and foxo6b in the developing brain and retina are transcriptionally regulated by PI3K signaling in zebrafish. Dev Genes Evol 227, 219–230 (2017). https://doi.org/10.1007/s00427-017-0575-6
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DOI: https://doi.org/10.1007/s00427-017-0575-6