Identification of the Cellular Mechanisms That Modulate Trafficking of Frizzled Family Receptor 4 (FZD4) Missense Mutants Associated With Familial Exudative Vitreoretinopathy

Milhem, Reham M.; Ben-Salem, Salma; Ali, Bassam R.

doi:10.1167/iovs.14-13885

Cited by 22 publications

(22 citation statements)

References 50 publications

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“…13 Likewise, Ells et al 16 Because relatives with the mutations did not have FEVR, the investigators concluded that these are milder mutations that may exacerbate retinopathy in premature infants. A potential mechanism for these milder FZD4 mutations was recently reported by Milhem et al 34 These investigators used confocal immunofluorescence microscopy to demonstrate localization of several FZD4 mutants, including P33S, in the endoplasmic reticulum when expressed in HeLa cells, indicating defective trafficking of the protein to the plasma membrane. They proposed that this defective trafficking may lead to haploinsufficiency of the frizzled-4 protein.…”

Section: Discussionmentioning

confidence: 92%

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation

et al. 2015

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Section: Discussionmentioning

confidence: 92%

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation

et al. 2015

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“…cac, which encodes a calcium channel, has seven human orthologs that also encode calcium channel subunits, of which CACNA1F has been associated with congenital night blindness (CSNB2A) (78), Aland Island eye disease (AIED) (79,80), and X-linked conerod dystrophy (CORDX3) (81). fz encodes a seven-transmembrane helix containing protein necessary for binding Wnt ligands in the noncanonical Wnt signaling pathway (82) and has 10 human orthologs encoding frizzled class receptors, of which FZD4 is associated with exudative vitreoretinopathy (83). hbn encodes a transcription factor and has four human orthologs, of which PHOX2A has been associated with congenital fibrosis of extraocular muscles, a disorder that affects the muscles that control eye movement and position of the eyes (84,85).…”

Section: Discussionmentioning

confidence: 99%

Genetic architecture of natural variation in visual senescence in Drosophila

Carbone

Yamamoto

Huang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Senescence, i.e., functional decline with age, is a major determinant of health span in a rapidly aging population, but the genetic basis of interindividual variation in senescence remains largely unknown. Visual decline and age-related eye disorders are common manifestations of senescence, but disentangling age-dependent visual decline in human populations is challenging due to inability to control genetic background and variation in histories of environmental exposures. We assessed the genetic basis of natural variation in visual senescence by measuring age-dependent decline in phototaxis using Drosophila melanogaster as a genetic model system. We quantified phototaxis at 1, 2, and 4 wk of age in the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and found an average decline in phototaxis with age. We observed significant genetic variation for phototaxis at each age and significant genetic variation in senescence of phototaxis that is only partly correlated with phototaxis. Genome-wide association analyses in the DGRP and a DGRP-derived outbred, advanced intercross population identified candidate genes and genetic networks associated with eye and nervous system development and function, including seven genes with human orthologs previously associated with eye diseases. Ninety percent of candidate genes were functionally validated with targeted RNAi-mediated suppression of gene expression. Absence of candidate genes previously implicated with longevity indicates physiological systems may undergo senescence independent of organismal life span. Furthermore, we show that genes that shape early developmental processes also contribute to senescence, demonstrating that senescence is part of a genetic continuum that acts throughout the life span.aging | behavioral genetics | DGRP GWA analysis | phototaxis | xQTL mapping

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“…Studies have shown that norrin-Fzd4 signaling affects angiogenesis in the female reproductive system. Markers for angiogenesis and vascular formation are reduced in the corpora lutea of Fzd4 null mice and these mice are infertile 42. Also, Fzd4 mRNA localizes to vessels and stroma surrounding the mouse embryo 43.…”

Section: Role Of Wnt Signaling In Fetal Developmentmentioning

confidence: 97%

Wnt signaling pathway in retinal vascularization

Drenser¹

2016

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Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence supports the importance of Wnt-signaling, and specifically, norrin-mediated Wnt-signaling in retinal development and retinal maintenance. Gene mutations affecting the Wnt-signaling pathways result in a variety of inherited vitreoretinopathies. Additionally, there is growing evidence that prematurity and associated retinopathy are associated with alterations in the Wnt-signaling pathways. Further investigations may allow for improved diagnoses, management, and therapies in the future.

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Identification of the Cellular Mechanisms That Modulate Trafficking of Frizzled Family Receptor 4 (FZD4) Missense Mutants Associated With Familial Exudative Vitreoretinopathy

Cited by 22 publications

References 50 publications

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation

Genetic architecture of natural variation in visual senescence in Drosophila

Wnt signaling pathway in retinal vascularization

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