Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate
            <i>Rax</i>
            expression

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

doi:10.1073/pnas.0710954105

Cited by 100 publications

(121 citation statements)

References 40 publications

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“…In a similar way, we observed mild or no cooperation between Sox2 and Pax6 or Otx2 on Six3.2 regulation (Fig. 3, F and G), in contrast to reports for other target genes (40,41). Furthermore, we could not find a previously proposed Six3 autoregulation (25,42), neither with Six3.2 nor with its Six3.1 paralog or their mammalian orthologue (Fig.…”

Section: Dose-response Luc Assays Confirmed Several Trs Candidates Ascontrasting

confidence: 48%

A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish

Beccari

Marco-Ferreres

Tabanera

et al. 2015

Journal of Biological Chemistry

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Background:The transcription factor Six3 is key element of forebrain specification, but its upstream regulators are unknown. Results: A systematic search in medaka fish identifies and functionally characterizes novel Six3 regulators. Conclusion:The spatio-temporal regulation of Six3 depends on a few trans-acting factors. Significance: This study provides new information on how forebrain neuronal diversity is originated.

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Section: Dose-response Luc Assays Confirmed Several Trs Candidates Ascontrasting

confidence: 48%

A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish

Beccari

Marco-Ferreres

Tabanera

et al. 2015

Journal of Biological Chemistry

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“…Sox2 and Otx2 are able to interact directly via their HMG and homeobox DNA-binding domains, respectively (Danno et al, 2008), and Otx2 has been shown to suppress the expression of Sox2 during retinal differentiation (Nishihara et al, 2012). The widespread ectopic expression of Sox2 in the cochlear duct of Pax2Cre-Otx2 mutant mice may suggest that it acts as a permissive prosensory factor allowing ectopic expression of Jag1 and p27 kip1 , which eventually generate an ectopic organ of Corti in the nonsensory region usually characterized by Otx2 expression.…”

Section: Discussionmentioning

confidence: 99%

Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea

et al. 2015

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Transcriptional regulatory networks are essential during the formation and differentiation of organs. The transcription factor N-myc is required for proper morphogenesis of the cochlea and to control correct patterning of the organ of Corti. We show here that the Otx2 gene, a mammalian ortholog of the Drosophila orthodenticle homeobox gene, is a crucial target of N-myc during inner ear development. Otx2 expression is lost in N-myc mouse mutants, and N-myc misexpression in the chick inner ear leads to ectopic expression of Otx2. Furthermore, Otx2 enhancer activity is increased by N-myc misexpression, indicating that N-myc may directly regulate Otx2. Inactivation of Otx2 in the mouse inner ear leads to ectopic expression of prosensory markers in non-sensory regions of the cochlear duct. Upon further differentiation, these domains give rise to an ectopic organ of Corti, together with the respecification of non-sensory areas into sensory epithelia, and the loss of Reissner's membrane. Therefore, the Otx2-positive domain of the cochlear duct shows a striking competence to develop into a mirrorimage copy of the organ of Corti. Taken together, these data show that Otx2 acts downstream of N-myc and is essential for patterning and spatial restriction of the sensory domain of the mammalian cochlea.

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“…To examine the subcellular localizations of the xRipply3 proteins, COS7 cells were transfected with 200 ng of pCS2-HA-xRipply3, and immunocytochemistry was performed as described previously (Danno et al, 2008) with an anti-HA antibody (Y-11; Santa Cruz Biotechnology).…”

Section: Cell Culturing Luciferase Assays Subcellular Localization mentioning

confidence: 99%

The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors

et al. 2009

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Bowline, which is a member of the Xenopus Bowline/Ripply family of proteins, represses the transcription of somitogenesis-related genes before somite segmentation, which makes Bowline indispensable for somitogenesis. Although there are three bowline/Ripply family genes in each vertebrate species, it is not known whether the Bowline/Ripply family proteins share a common role in development. To elucidate their developmental roles, we examined the expression patterns and functions of the Xenopus Bowline/Ripply family proteins Bowline, Ledgerline, and a novel member of this protein family, xRipply3. We found that the expression patterns of bowline and ledgerline overlapped in the presomitic mesoderm (PSM), whereas ledgerline was additionally expressed in the newly formed somites. In addition, we isolated xRipply3, which is expressed in the pharyngeal region. Co-immunoprecipitation assays revealed that Ledgerline and xRipply3 interacted with T-box proteins and the transcriptional co-repressor Groucho/TLE. In luciferase assays, xRipply3 weakly suppressed the transcriptional activity of Tbx1, while Ledgerline strongly suppressed that of Tbx6. In line with the repressive role of Ledgerline, knockdown of Ledgerline resulted in enlargement of expression regions of the somitogenesis-related-genes mespb and Tbx6. Inhibition of histone deacetylase activity increased the expression of mespb, as seen in the Bowline and Ledgerline knockdown experiments. These results suggest that the Groucho-HDAC complex is required for the repressive activity of Bowline/Ripply family proteins during Xenopus somitogenesis. We conclude that although the Xenopus Bowline/Ripply family proteins Bowline, Ledgerline and xRipply3 are expressed differentially, they all act as negative regulators of T-box proteins.

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Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

Cited by 100 publications

References 40 publications

A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish

A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish

Otx2 is a target of N-myc and acts as a suppressor of sensory development in the mammalian cochlea

The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors

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