Autosomal Recessive Familial Exudative Vitreoretinopathy Is Associated with Mutations in LRP5

Jiao, Xiaodong; Ventruto, V; Trese, Michael T.; Shastry, Barkur S.; Hejtmancik, J. F.

doi:10.1086/425080

Cited by 170 publications

(125 citation statements)

References 31 publications

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“…Second, mice lacking either of the Frizzled co-receptors (LRP5 or LRP6) demonstrated abnormal eye development. LRP6 knockout mice were microophthalmic and had severe defects in their retinal, lens, and corneal development (Gong et al, 2001;Stump et al, 2003;Jiao et al, 2004;Toomes et al, 2004). In LRP5 knockout mice, the hyaloid vasculature did not regress and was retained throughout the lifetime of the mice (Gong et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Expression patterns of Wnt genes during development of an anterior part of the chicken eye

Fokina

Frolova

2005

Developmental Dynamics

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To address the roles of Wnts in the development of the anterior eye, we used a chicken model to perform comprehensive expression analysis of all Wnt genes during anterior eye development. In analyzing the available genomic sequences, we found that the chicken genome encodes 18 Wnt proteins that are homologous to corresponding human and mouse proteins. The mRNA sequences for 12 chicken Wnt genes are available in GenBank, and mRNAs for six other Wnt genes (Wnt2, Wnt5b, Wnt7b, Wnt8b, Wnt9b, and Wnt16) were identified and cloned based on the homology to the genes from other species. In addition, we found that chicken Wnt3a and Wnt7b genes encode two alternative mRNA isoforms containing different first exons. Following in situ hybridization, we found that out of 18 Wnt genes, 11 genes were expressed in the anterior eye, exhibiting distinct temporal-spatial patterns. Several Wnts were expressed in the lens, including Wnt2 and Wnt2b in the anterior epithelium and Wnt5a, Wnt5b, Wnt7a, and Wnt7b in the differentiating lens fiber cells. In the cornea, we detected Wnt3a, Wnt6, and Wnt9b in the ocular surface ectoderm, including the corneal epithelium, and Wnt9a in the corneal endothelium from the onset of its differentiation. In the optic cup, Wnt2, Wnt2b, and Wnt9a were localized in the rim of the optic cup (presumptive iris), while Wnt5a and Wnt16 were detected in the ciliary epithelium/iris zone of the differentiated optic cup, and Wnt6 was expressed in the iridial mesenchyme. These data suggest that Wnt signaling might play important roles in anterior eye development. Developmental Dynamics 235: 496 -505, 2006.

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Section: Introductionmentioning

confidence: 99%

Expression patterns of Wnt genes during development of an anterior part of the chicken eye

Fokina

Frolova

2005

Developmental Dynamics

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“…Some studies suggest that FZD4 signals through an alternative (Ca 21 ) Wnt pathway (Robitaille et al 2002). However, the finding that the mutations in the Wnt coreceptor LRP ( Jiao et al 2004;Toomes et al 2004a), which is implicated in Arm/b-catenin signaling and not in the Ca 21 pathway, also cause FEVR does not support this model. Moreover, FZD4 in collaboration with LRP5 can be stimulated to activate Arm/b-catenin signaling by Norrin, a non-Wnt ligand that binds to the CRD (Xu et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Genetic Evidence That Drosophila frizzled Controls Planar Cell Polarity and Armadillo Signaling by a Common Mechanism

et al. 2005

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The frizzled ( fz) gene in Drosophila controls two distinct signaling pathways: it directs the planar cell polarization (PCP) of epithelia and it regulates cell fate decisions through Armadillo (Arm) by acting as a receptor for the Wnt protein Wingless (Wg). With the exception of dishevelled (dsh), the genes functioning in these two pathways are distinct. We have taken a genetic approach, based on a series of new and existing fz alleles, for identifying individual amino acids required for PCP or Arm signaling. For each allele, we have attempted to quantify the strength of signaling by phenotypic measurements. For PCP signaling, the defect was measured by counting the number of cells secreting multiple hairs in the wing. We then examined each allele for its ability to participate in Arm signaling by the rescue of fz mutant embryos with maternally provided fz function. For both PCP and Arm signaling we observed a broad range of phenotypes, but for every allele there is a strong correlation between its phenotypic strength in each pathway. Therefore, even though the PCP and Arm signaling pathways are genetically distinct, the set of signalingdefective fz alleles affected both pathways to a similar extent. This suggests that fz controls these two different signaling activities by a common mechanism. In addition, this screen yielded a set of missense mutations that identify amino acids specifically required for fz signaling function.A NIMAL development requires the interplay between cell fate decisions and morphogenetic events. It is not well understood how cell fate decisions, which are the outcome of changes in gene regulation, are coordinated with changes in morphology, such as cell movement, shape change, and polarization. The frizzled ( fz) gene in Drosophila has the remarkable ability to control both cell fate decisions and the planar polarization of epithelia. What makes fz exceptional is that it interacts with two distinct signaling cascades to accomplish these functions. We are trying to understand the mechanism that regulates the switch between these two pathways. Uncovering how fz chooses between these two functions will provide insight into how morphogenesis and cell fate choices are orchestrated.

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“…The present result provides evidence that X-linked recessive CMN and Xlinked dominant CMN may be caused by the same gene with different mutations. Different mutations in the same gene causing a similar phenotype but with a different pattern of inheritance have been identified in several genes related to ocular diseases, e.g., RP1 (Khaliq et al 2005;Riazuddin et al 2005;Sullivan et al 1999), RHO (Dryja et al 1990;Rosenfeld et al 1992), LRP5 (Jiao et al 2004;Toomes et al 2004), etc. On the other hand, linkage to the same region does not rule out the possibility that the disease may result from mutation of different genes (Toomes et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Linkage analysis of two families with X-linked recessive congenital motor nystagmus

Guo

Jia

et al. 2005

J Hum Genet

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X-linked recessive congenital motor nystagmus was identified in two Chinese families living in the Guangdong province of China. Nystagmus was noticed in early childhood. Only males in the families were affected and all obligate carriers did not have nystagmus. Linkage study was performed using microsatellite markers at about 10 cM intervals on the X chromosome. The nystagmus in these two families is linked to markers in the region of chromosome Xq23-q27, including DXS1001, DXS8009, and DXS1047. DXS1047 gave the highest lod score of 3.53 at h=0.

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Autosomal Recessive Familial Exudative Vitreoretinopathy Is Associated with Mutations in LRP5

Cited by 170 publications

References 31 publications

Expression patterns of Wnt genes during development of an anterior part of the chicken eye

Expression patterns of Wnt genes during development of an anterior part of the chicken eye

Genetic Evidence That Drosophila frizzled Controls Planar Cell Polarity and Armadillo Signaling by a Common Mechanism

Linkage analysis of two families with X-linked recessive congenital motor nystagmus

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