Xrxl, a novel Xenopus homeobox gene expressed during eye and pineal gland development

Casarosa, Simona; Andreazzoli, Massimiliano; Simeone, Antonio; Barsacchi, Giuseppina

doi:10.1016/s0925-4773(96)00640-5

Cited by 142 publications

(140 citation statements)

References 52 publications

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“…The xAmer2 probe was generated from the cDNA clone IRAKp961P02150Q in pCMV-Sport6. The En-2 (engrailed 2), Rx1, and Sox2 probes were described previously (13)(14)(15)(16).…”

Section: Methodsmentioning

confidence: 99%

Amer2 Protein Is a Novel Negative Regulator of Wnt/β-Catenin Signaling Involved in Neuroectodermal Patterning

Pfister

Tanneberger

Schambony

et al. 2012

Journal of Biological Chemistry

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“…The xAmer2 probe was generated from the cDNA clone IRAKp961P02150Q in pCMV-Sport6. The En-2 (engrailed 2), Rx1, and Sox2 probes were described previously (13)(14)(15)(16).…”

Section: Methodsmentioning

confidence: 99%

Amer2 Protein Is a Novel Negative Regulator of Wnt/β-Catenin Signaling Involved in Neuroectodermal Patterning

Pfister

Tanneberger

Schambony

et al. 2012

Journal of Biological Chemistry

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“…A 800-base-pair fragment from Sox3 was cloned into pGEMT-easy, transcribed with Sp6 RNA polymerase and linearized with SacII. Clones containing the templates for Pax6, Rx1, Six3 and Otx2 were generated in accordance with published protocols 4,[32][33][34] . The probe was labelled by using a digoxigenin labelling kit (Roche) and the hybridization was revealed with sheep anti-digoxigenin-alkaline phosphatase antibody (Roche) and 4-nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolylphosphate substrate (NBT/BCIP; Roche).…”

Section: Methodsmentioning

confidence: 99%

Purine-mediated signalling triggers eye development

Massé

Bhamra

Eason

et al. 2007

Nature

126

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A conserved network of eye field transcription factors (EFTFs) underlies the development of the eye in vertebrates and invertebrates 1 . To direct eye development, Pax6, a key gene in this network 2,3 , interacts with genes encoding other EFTFs such as . However, the mechanisms that control expression of the EFTFs remain unclear 7 . Here we show that purine-mediated signalling triggers both EFTF expression and eye development in Xenopus laevis. Overexpression of ectonucleoside triphosphate diphosphohydrolase 2 (E-NTPDase2) 8 , an ectoenzyme that converts ATP to ADP 9 , caused ectopic eye-like structures, with occasional complete duplication of the eye, and increased expression of Pax6, Rx1 and Six3. In contrast, downregulation of endogenous E-NTPDase2 decreased Rx1 and Pax6 expression. E-NTPDase2 therefore acts upstream of these EFTFs. To test whether ADP (the product of E-NTPDase2) might act to trigger eye development through P2Y1 receptors, selective in Xenopus for ADP 10,11 , we simultaneously knocked down expression of the genes encoding E-NTPDase2 and the P2Y1 receptor. This could prevent the expression of Rx1 and Pax6 and eye formation completely. We next measured ATP release 12-14 in the presumptive eye field, demonstrating a transient release of ATP at a time that could plausibly trigger (once converted to ADP) expression of the EFTFs. This surprising role for transient purinemediated signalling in eye development may be widely conserved, because alterations to the locus of E-NTPDase2 on human chromosome 9 cause severe head and eye defects, including microphthalmia [15][16][17][18] . Our results suggest a new mechanism for the initiation of eye development.To assess the developmental functions of the E-NTPDases, we simultaneously injected the mRNA for the closely related ENTPDases1-3 (ref. 8) with lineage tracer into a dorsal animal blastomere at the eight-cell stage to target overexpression of this gene to one side of the nervous system. Overexpression of E-NTPDase2 affected eye development in 27 of 41 embryos, causing in some cases complete duplication of the eye on the injected side (Fig. 1A, a). In contrast, overexpression of E-NTPDase1 decreased eye size (11 of 44 embryos; Fig. 1A, b), whereas overexpression of E-NTPDase3 gave a weaker phenotype somewhat similar to that of E-NTPDase2 (4 of 42 embryos, Fig. 1A, c, Supplementary Tables 1a and 2). E-NTPDases differ in their catalytic activity. Like their mammalian orthologues, E-NTPDase1 can metabolize ATP and ADP with roughly equal efficacy, E-NTPDase2 is highly selective for ATP and hardly metabolizes ADP, and E-NTPDase3 has intermediate selectivity for ATP and ADP ( Supplementary Fig. 2). The phenotypes elicited by overexpression of these membrane-bound E-NTPDases correlate with their capacity to metabolize ADP.The eye phenotypes caused by overexpression of E-NTPDase2 (Supplementary Table 1b) included the following: disrupted eye development (Fig. 1A, d); ectopic retinal pigment epithelium (RPE) (Fig. 1A, e); RPE extensions (Fig. 1A, f); and ectopic...

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“…Recently a small family of paired-like homeobox genes that is critical for eye formation, the Rx/Rax (for Retinal homeobox) family, has been identified (Casarosa et al, 1997;Eggert et al, 1998;Furukawa et al, 1997b;Loosli et al, 2001;Mathers et al, 1997;Ohuchi et al, 1999).…”

Section: Initial Stages Of Vertebrate Eye Developmentmentioning

confidence: 99%

“…One of the most interesting genes isolated by this approach was the novel, paired-like homeobox gene Rx (for Retinal homeobox) (Mathers et al, 1997). Xrx was also independently isolated by Casarosa et al, (1997) from a stage 24/25 Xenopus cDNA library by screening with the murine Orthopedia probe.…”

Section: Expression Pattern Of Xenopus Rx Genesmentioning

confidence: 99%

Regulation of vertebrate eye development by Rx genes

Bailey

El‐Hodiri²,

Zhang³

et al. 2004

Int. J. Dev. Biol.

160

127

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The paired-like homeobox-containing gene Rx has a critical role in the eye development of several vertebrate species including Xenopus, mouse, chicken, medaka, zebrafish and human. Rx is initially expressed in the anterior neural region of developing embryos, and later in the retina and ventral hypothalamus. Abnormal regulation or function of Rx results in severe abnormalities of eye formation. Overexpression of Rx in Xenopus and zebrafish embryos leads to overproliferation of retinal cells. A targeted elimination of Rx in mice results in a lack of eye formation. Mutations in Rx genes are the cause of the mouse mutation eyeless (ey1), the medaka temperature sensitive mutation eyeless (el) and the zebrafish mutation chokh. In humans, mutations in Rx lead to anophthalmia. All of these studies indicate that Rx genes are key factors in vertebrate eye formation. Because these results cannot be easily reconciled with the most popular dogmas of the field, we offer our interpretation of eye development and evolution.

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Xrxl, a novel Xenopus homeobox gene expressed during eye and pineal gland development

Cited by 142 publications

References 52 publications

Amer2 Protein Is a Novel Negative Regulator of Wnt/β-Catenin Signaling Involved in Neuroectodermal Patterning

Amer2 Protein Is a Novel Negative Regulator of Wnt/β-Catenin Signaling Involved in Neuroectodermal Patterning

Purine-mediated signalling triggers eye development

Regulation of vertebrate eye development by Rx genes

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