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      WNT/β-Catenin Signaling in Vertebrate Eye Development

      review-article
      Frontiers in Cell and Developmental Biology
      Frontiers Media S.A.
      retina, WNT, β-catenin, development, differentiation

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          Abstract

          The vertebrate eye is a highly specialized sensory organ, which is derived from the anterior neural plate, head surface ectoderm, and neural crest-derived mesenchyme. The single central eye field, generated from the anterior neural plate, divides to give rise to the optic vesicle, which evaginates toward the head surface ectoderm. Subsequently, the surface ectoderm, in conjunction with the optic vesicle invaginates to form the lens vesicle and double-layered optic cup, respectively. This complex process is controlled by transcription factors and several intracellular and extracellular signaling pathways including WNT/β-catenin signaling. This signaling pathway plays an essential role in multiple developmental processes and has a profound effect on cell proliferation and cell fate determination. During eye development, the activity of WNT/β-catenin signaling is tightly controlled. Faulty regulation of WNT/β-catenin signaling results in multiple ocular malformations due to defects in the process of cell fate determination and differentiation. This mini-review summarizes recent findings on the role of WNT/β-catenin signaling in eye development. Whilst this mini-review focuses on loss-of-function and gain-of-function mutants of WNT/β-catenin signaling components, it also highlights some important aspects of β-catenin-independent WNT signaling in the eye development at later stages.

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          Most cited references67

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          Secreted and transmembrane wnt inhibitors and activators.

          Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease.
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            Mouse small eye results from mutations in a paired-like homeobox-containing gene.

            Small eye (Sey) in mouse is a semidominant mutation which in the homozygous condition results in the complete lack of eyes and nasal primordia. On the basis of comparative mapping studies and on phenotypic similarities, Sey has been suggested to be homologous to congenital aniridia (lack of iris) in human. A candidate gene for the aniridia (AN) locus at 11p13 has been isolated by positional cloning and its sequence and that of the mouse homologue has been established (C.T., manuscript in preparation). This gene belongs to the paired-like class of developmental genes first described in Drosophila which contain two highly conserved motifs, the paired box and the homeobox. In vertebrates, genes which encode the single paired domain as well as those which express both motifs have been described as the Pax multigene family. A Pax gene recently described as Pax-6 is identical to the mouse homologue of the candidate aniridia gene. Here we report the analysis of three independent Sey alleles and show that indeed this gene is mutated and that the mutations would predictably interrupt gene function.
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              Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease.

              The secreted Frizzled-related proteins (SFRPs) are a family of soluble proteins that are structurally related to Frizzled (Fz) proteins, the serpentine receptors that mediate the extensively used cell-cell communication pathway involving Wnt signalling. Because of their homology with the Wnt-binding domain on the Fz receptors, SFRPs were immediately characterised as antagonists that bind to Wnt proteins to prevent signal activation. Since these initial studies, interest in the family of SFRPs has grown progressively, offering new perspectives on their function and mechanism of action in both development and disease. These studies indicate that SFRPs are not merely Wnt-binding proteins, but can also antagonise one another's activity, bind to Fz receptors and influence axon guidance, interfere with BMP signalling by acting as proteinase inhibitors, and interact with other receptors or matrix molecules. Furthermore, their expression is altered in different types of cancers, bone pathologies, retinal degeneration and hypophosphatemic diseases, indicating that their activity is fundamental for tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt interactions and discuss the new and emerging roles of SFRPs.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                30 November 2016
                2016
                : 4
                : 138
                Affiliations
                Laboratory of Eye Biology, BIOCEV Division, Institute of Molecular Genetics Prague, Czechia
                Author notes

                Edited by: Andrea Erika Münsterberg, University of East Anglia, UK

                Reviewed by: Paola Bovolenta, Spanish National Research Council, Spain; Gunnar Schulte, Karolinska Institutet, Sweden; Andrea Streit, King's College London, UK

                *Correspondence: Naoko Fujimura fujimura@ 123456img.cas.cz

                This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2016.00138
                5127792
                27965955
                f09a7e78-ee79-430f-8520-661ea2b56ed6
                Copyright © 2016 Fujimura.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 August 2016
                : 09 November 2016
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 78, Pages: 7, Words: 6159
                Funding
                Funded by: Ministerstvo Školství, Mládeže a Tělovýchovy 10.13039/501100001823
                Categories
                Cell and Developmental Biology
                Mini Review

                retina,wnt,β-catenin,development,differentiation
                retina, wnt, β-catenin, development, differentiation

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