Both ciliary and non-ciliary functions of Foxj1a confer Wnt/β-catenin signaling in zebrafish left-right patterning

Zhu, Ping; Xu, Xiaolei; Lin, Xueying

doi:10.1242/bio.012088

Cited by 17 publications

(13 citation statements)

References 72 publications

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“…Downregulation of cWnt/β-catenin leads to depletion of Lef1 and Tcf7, inhibiting foxj1a transcription. This results in shorter and fewer cilia with loss of cilia motility that can be rescued with overexpression foxj1a (Lin and Xu, 2009;Caron et al, 2012;Zhu et al, 2015). Dvl has also been shown to interact with DCDC2, which binds to tubulin to enhance microtubule polymerization and localizes to the ciliary axoneme (Schueler et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

et al. 2018

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MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expressions by binding to the 3′ untranslated region of target mRNAs thereby silencing translation. Some miRNAs are key regulators of the Wnt signaling pathways, which impact developmental processes. This study investigates miRNA regulation of different isoforms of Dishevelled (Dvl/Dsh), which encode a key component in the Wnt signaling pathway. The sea urchin Dvl mRNA isoforms have similar spatial distribution in early development, but one isoform is distinctively expressed in the larval ciliary band. We demonstrated that Dvl isoforms are directly suppressed by miRNAs. By blocking miRNA suppression of Dvl isoforms, we observed dosedependent defects in spicule length, patterning of the primary mesenchyme cells, gut morphology, and cilia. These defects likely result from increased Dvl protein levels, leading to perturbation of Wnt-dependent signaling pathways and additional Dvl-mediated processes. We further demonstrated that overexpression of Dvl isoforms recapitulated some of the Dvl miRNATP-induced phenotypes. Overall, our results indicate that miRNA suppression of Dvl isoforms plays an important role in ensuring proper development and function of primary mesenchyme cells and cilia.

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Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

et al. 2018

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“…Wnt signaling regulates ciliogenesis in zebrafish via Foxj1a, a ciliogenic transcription factor, and later contributes to proper left-sided Nodal gene expression by repressing repression of Nodal (H€ usken and Carl, 2013). Inhibition of Foxj1a transcription leads to a reduction of cilia length and number and randomized asymmetry (Zhu et al, 2015).…”

Section: Asymmetry Paysmentioning

confidence: 99%

Ontogenesis of Lateralization

Güntürkün

Ocklenburg

2017

Neuron

176

150

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The brains of humans and other animals are asymmetrically organized, but we still know little about the ontogenetic and neural fundaments of lateralizations. Here, we review the current state of understanding about the role of genetic and non-genetic factors for the development of neural and behavioral asymmetries in vertebrates. At the genetic level, the Nodal signaling cascade is of central importance, but several other genetic pathways have been discovered to also shape the lateralized embryonic brain. Studies in humans identified several relevant genes with mostly small effect sizes but also highlight the extreme importance of non-genetic factors for asymmetry development. This is also visible in visual asymmetry in birds, in which genes only affect embryonic body position, while the resulting left-right difference of visual stimulation shapes visual pathways in a lateralized way. These and further studies in zebrafish and humans highlight that the many routes from genes to asymmetries of function run through left-right differences of neural pathways. They constitute the lateralized blueprints of our perception, cognition, and action.

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“…For example, FOXM1 and FOXQ1 are both targets of the Wnt/β-catenin pathway [ 30 , 31 ], and these 2 transcriptors are also both believed to be activators of the Wnt/β-catenin pathway [ 32 , 33 ]. In physiological circumstances, FOXJ1 is also a direct target activated by the Wnt/β-catenin signaling in Kupffer’s vesicles of zebrafish [ 34 , 35 ]. However, in lung morphogenesis, FOXJ activates the Wnt/β-catenin antagonist chibby [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Forkhead Box Protein J1 (FOXJ1) is Overexpressed in Colorectal Cancer and Promotes Nuclear Translocation of β-Catenin in SW620 Cells

Liu

Fan

2017

Med Sci Monit

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BackgroundFOXJ1, which is a forkhead transcription factor, has been previously studied mostly as a ciliary transcription factor. The role of FOXJ1 in cancer progression is still elusive and controversial. In the present study, the effect of FOXJ1 in progression of colorectal cancer (CRC) was investigated.Material/MethodsThe pattern of FOXJ1 expression was investigated using the method of immunohistochemistry (IHC) in a tissue microarray (TMA) incorporating 50 pairs of colon cancer specimens and adjacent normal tissue. In addition, the correlation of FOXJ1 expression with clinicopathological characteristics was evaluated in the other TMA containing 208 cases of colon cancer. Moreover, the influence of regulating FOXJ1 level on the proliferation, migration, and invasion ability of colorectal cancer (CRC) cells was evaluated.ResultsIncreased expression of FOXJ1was significantly associated with clinical stage (p<0.05), metastasis of lymph node (p<0.05), and invasion depth (p<0.001) in colon cancer, suggesting FOXJ1 is a tumor promoter in CRC. Consistently, FOXJ1 overexpression significantly enhanced the proliferation, migration, and invasion of CRC cells, while silencing of FOXJ1 induced the opposite effect. Furthermore, up-regulation of FOXJ1 in SW620 cells markedly inhibited the level of truncated APC and the phosphorylation of β-catenin, while the level of cyclinD1 was decreased. In addition, overexpression of FOXJ1 significantly promoted nuclear translocation of β-catenin in SW620 cells.ConclusionsThese findings demonstrate that increased FOXJ1 contributes to the progression of CRC, which might be associated with the promotion effect of β-catenin nuclear translocation. FOXJ1 may be a novel therapeutic target in CRC.

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Both ciliary and non-ciliary functions of Foxj1a confer Wnt/β-catenin signaling in zebrafish left-right patterning

Cited by 17 publications

References 72 publications

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

Inhibition of microRNA suppression of Dishevelled results in Wnt pathway-associated developmental defects in sea urchin

Ontogenesis of Lateralization

Forkhead Box Protein J1 (FOXJ1) is Overexpressed in Colorectal Cancer and Promotes Nuclear Translocation of β-Catenin in SW620 Cells

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