<i>Rx‐Cre</i>, a tool for inactivation of gene expression in the developing retina

Swindell, Eric C.; Bailey, Travis J.; Loosli, Felix; Liu, Chaomei; Amaya-Manzanares, Felipe; Mahon, Kathleen; Wittbrodt, Joachim; Jamrich, Milan

doi:10.1002/dvg.20225

Cited by 75 publications

(113 citation statements)

References 12 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…Similar coloboma and optic disc defects were also observed in Rx-Cre;Fgfr1 flox/flox ; Fgfr2 flox/flox double mutants, where Fgfr1 and Fgfr2 were ablated using another retina-specific Cre driver, Rx-Cre (supplementary material Fig. S2) (Swindell et al, 2006). Taken together, our histological and molecular analyses suggest that ectopic pigmentation of optic fissure in Fgfr mutants caused ocular coloboma by preventing the fusion of the ventral optic vesicle.…”

Section: Research Articlesupporting

confidence: 79%

“…Six3-Cre mice were kindly provided by Dr Yasuhide Furuta (MD Anderson Cancer Center, Houston, TX, USA) (Furuta et al, 2000). Rx-Cre mice were kindly provided by Dr Milan Jamrich (Baylor College of Medicine, Houston, TX, USA) (Swindell et al, 2006). LSLKras G12D mice were obtained from the Mouse Models of Human Cancers Consortium (MMHCC) Repository at National Cancer Institute (Tuveson et al, 2004).…”

Section: Fmentioning

confidence: 99%

See 1 more Smart Citation

Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma

Cai

Tao

et al. 2013

Development

View full text Add to dashboard Cite

SUMMARYFGF signaling plays a pivotal role in eye development. Previous studies using in vitro chick models and systemic zebrafish mutants have suggested that FGF signaling is required for the patterning and specification of the optic vesicle, but due to a lack of genetic models, its role in mammalian retinal development remains elusive. In this study, we show that specific deletion of Fgfr1 and Fgfr2 in the optic vesicle disrupts ERK signaling, which results in optic disc and nerve dysgenesis and, ultimately, ocular coloboma. Defective FGF signaling does not abrogate Shh or BMP signaling, nor does it affect axial patterning of the optic vesicle. Instead, FGF signaling regulates Mitf and Pax2 in coordinating the closure of the optic fissure and optic disc specification, which is necessary for the outgrowth of the optic nerve. Genetic evidence further supports that the formation of an Frs2α-Shp2 complex and its recruitment to FGF receptors are crucial for downstream ERK signaling in this process, whereas constitutively active Ras signaling can rescue ocular coloboma in the FGF signaling mutants. Our results thus reveal a previously unappreciated role of FGF-Frs2α-Shp2-Ras-ERK signaling axis in preventing ocular coloboma. These findings suggest that components of FGF signaling pathway may be novel targets in the diagnosis of and the therapeutic interventions for congenital ocular anomalies.

show abstract

Section: Research Articlesupporting

confidence: 79%

Section: Fmentioning

confidence: 99%

Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma

Cai

Tao

et al. 2013

Development

View full text Add to dashboard Cite

show abstract

“…PCR analysis of genomic DNA from NR and RPE/choroid (RPE-Ch) samples, obtained from at least 30 control (Dnmt1 fl/fl ) and mutant (Dnmt1 fl/fl :Rx-Cre/+) mice at different developmental stages, revealed the predicted excision of exons 4 and 5 (Jackson-Grusby et al, 2001); the excision is more efficient in NR (>95% in most animals at all ages) than in RPE-Ch (Fig. 1D), presumably because the Rx-Cre transgene is expressed in RPE but not in the contaminating choroidal tissue (Swindell et al, 2006) (a representative blot is shown in Fig. 1D).…”

Section: Bisulfite Pyrosequencingmentioning

confidence: 95%

“…The small size of the mice could be due to hormonal insufficiency (Nasonkin et al, 2004) resulting from RxCre activity in the ventral hypothalamus/posterior pituitary in addition to the developing eye (Swindell et al, 2006;MedinaMartinez et al, 2009). However, the small eye phenotype of Dnmt1 fl/fl :Rx-Cre/+ mice is likely to be a consequence of the expression of mutant Dnmt1 in the NR and RPE rather than a result of hypothalamic insufficiency, as hypopituitary Prop1 df/df mice have normal sized eyes (data not shown) and a normal rod:cone ratio (supplementary material Fig.…”

Section: Research Articlementioning

confidence: 99%

Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

et al. 2013

Self Cite

View full text Add to dashboard Cite

SUMMARYDysfunction or death of photoreceptors is the primary cause of vision loss in retinal and macular degenerative diseases. As photoreceptors have an intimate relationship with the retinal pigment epithelium (RPE) for exchange of macromolecules, removal of shed membrane discs and retinoid recycling, an improved understanding of the development of the photoreceptor-RPE complex will allow better design of gene-and cell-based therapies. To explore the epigenetic contribution to retinal development we generated conditional knockout alleles of DNA methyltransferase 1 (Dnmt1) in mice. Conditional Dnmt1 knockdown in early eye development mediated by Rx-Cre did not produce lamination or cell fate defects, except in cones; however, the photoreceptors completely lacked outer segments despite near normal expression of phototransduction and cilia genes. We also identified disruption of RPE morphology and polarization as early as E15.5. Defects in outer segment biogenesis were evident with Dnmt1 exon excision only in RPE, but not when excision was directed exclusively to photoreceptors. We detected a reduction in DNA methylation of LINE1 elements (a measure of global DNA methylation) in developing mutant RPE as compared with neural retina, and of Tuba3a, which exhibited dramatically increased expression in mutant retina. These results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. We also establish a model to study the epigenetic mechanisms and signaling pathways that guide the modulation of photoreceptor outer segment morphogenesis by RPE during retinal development and disease.

show abstract

“…Whereas in higher vertebrates the requirement for signaling from the optic vesicle during lens induction is well demonstrated (Brownell et al, 2000;Kamachi et al, 1998;Mathers et al, 1997;Porter et al, 1997;Swindell et al, 2006), in lower vertebrates, such as frog and salmon, lens formation without the formation of the retina has been reported (Mencl, 1903;Spemann, 1912). How the lens develops in these species in the absence of the retina is not understood.…”

Section: Lens Induction: the Tissues Involvedmentioning

confidence: 99%

Foxe view of lens development and disease

Medina-Martínez

Jamrich

2007

Development

Self Cite

View full text Add to dashboard Cite

The recent identification of a mutation in Foxe3 that causes congenital primary aphakia in humans marks an important milestone. Congenital primary aphakia is a rare developmental disease in which the lens does not form. Previously, Foxe3 had been shown to play a crucial role in vertebrate lens formation and this gene is one of the earliest integrators of several signaling pathways that cooperate to form a lens. In this review, we highlight recent advances that have led to a better understanding of the developmental processes and gene regulatory networks involved in lens development and disease.

show abstract

Rx‐Cre, a tool for inactivation of gene expression in the developing retina

Cited by 75 publications

References 12 publications

Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma

Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma

Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

Foxe view of lens development and disease

Contact Info

Product

Resources

About