Zebrafish Olfactomedin 1 Regulates Retinal Axon Elongation<i>In Vivo</i>and Is a Modulator of Wnt Signaling Pathway

Nakaya, Naoki; Lee, Hee‐Sheung; Takada, Yuji; Tzchori, Itai; Tomarev, Stanislav I.

doi:10.1523/jneurosci.0617-08.2008

Cited by 52 publications

(71 citation statements)

References 43 publications

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“…Our previous results indicated that other members of the family of olfactomedindomain-containing proteins, olfactomedin 1 and olfactomedin 3, also known as optimedin, showed some similarities to the action of Wnt proteins (46,58). Therefore, we tested whether myocilin may act through components of Wnt signaling pathways.…”

Section: Resultsmentioning

confidence: 98%

“…Currently, we do not know whether full-length myocilin and myocilin-⌬C perform different biological functions. It has been reported that different forms of olfactomedin 1, with or without the olfactomedin domain, may have distinct roles in neuronal differentiation (55,58).…”

Section: Discussionmentioning

confidence: 99%

“…Olfactomedin domain was originally identified in a glycoprotein isolated from the olfactory epithelium of frogs (71) and subsequently was found in a group of proteins forming a family of olfactomedin domaincontaining proteins. The family of olfactomedin domain-containing proteins includes both secreted and membrane-bound proteins that each exhibit a characteristic distribution in different tissues (4,10,27,30,44,51,58,78,79). Most of the glaucomacausing mutations in myocilin are located in the olfactomedin domain (1,2,18,19,24,72).…”

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Myocilin Is a Modulator of Wnt Signaling

Kwon

Lee

et al. 2009

Molecular and Cellular Biology

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It is well documented that mutations in the MYOCILINGlaucoma is a leading cause of blindness in the world. Primary open-angle glaucoma is the most common form of glaucoma. It will affect more than 60 million and blind about 4.5 million people worldwide by the year 2010 (62). It is now well established that a genetic component may contribute to glaucoma, and several glaucoma-associated genes have been identified. The first-identified and the most-studied gene is MYOCILIN (MYOC), which is highly expressed in and secreted by the trabecular meshwork (1,19,72,75,77,78), one of the key components of the eye aqueous humor outflow system. Dominant mutations in MYOC may lead to juvenile openangle glaucoma and are found in 3 to 4% of patients with primary open-angle glaucoma (18,19). The encoded protein, myocilin, belongs to a family of glycosylated proteins containing a C-terminal olfactomedin domain (57,90,91). Olfactomedin domain was originally identified in a glycoprotein isolated from the olfactory epithelium of frogs (71) and subsequently was found in a group of proteins forming a family of olfactomedin domaincontaining proteins. The family of olfactomedin domain-containing proteins includes both secreted and membrane-bound proteins that each exhibit a characteristic distribution in different tissues (4,10,27,30,44,51,58,78,79). Most of the glaucomacausing mutations in myocilin are located in the olfactomedin domain (1,2,18,19,24,72).Besides the trabecular meshwork and sclera (1, 77), high levels of MYOC were observed in the ciliary body (1, 13, 39), iris (89), retinal pigment epithelium/choroid (78, 88), and optic nerve (74). Low levels of MYOC expression were detected in several nonocular tissues (75). Myocilin, being a secreted protein, was also found in the aqueous humor, an intraocular fluid responsible for the supply of nutrients and for removal of metabolites from the avascular tissues of the eye anterior segment (63, 65). Some mutations in the MYOC gene lead to the inhibition of mutated myocilin secretion. Secretion of wildtype myocilin also can be reduced or blocked in the presence of mutated myocilin (22,36,52). It has been suggested that the intracellular accumulation of myocilin aggregates is deleterious to the trabecular meshwork cells, resulting in the deterioration of their function and subsequent elevation of intraocular pressure (IOP) (38,49).Although the MYOC gene has been studied for more than 10 years, the functions of myocilin protein are still not well understood (19,75). Biochemical data indicate that myocilin may interact with several intracellular and extracellular matrix proteins (16,37,48,61,73,78), although the biological significance of such interactions is not clear. The absence of openangle glaucoma in an elderly woman homozygous for the Arg46Stop mutation (45), as well as the absence of glaucoma in people hemizygous for MYOC (87), suggests that the loss of functional myocilin is not critical for the development of glaucoma or for normal eye functioning. These observations are supporte...

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Myocilin Is a Modulator of Wnt Signaling

Kwon

Lee

et al. 2009

Molecular and Cellular Biology

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“…Wif protein consists of an N-terminal secretion signal sequence (NT), the WIF domain (WD), epidermal growth factor-like repeats (EGFs) and a hydrophilic C-terminus. Human WIF1 binds through its WD to Drosophila Wg, to zebrafish and Xenopus Wnt8 (Hsieh et al, 1999;Kawano and Kypta, 2003), to eight Wnts (including 3a, 4, 5a, 7a, 9a, 11) (Surmann-Schmitt et al, 2009), and to a protein involved in neuronal differentiation, olfactomedin 1 (Nakaya et al, 2008). However, a recent report has shown that human WIF1 binds to Wnts both through the WD and the EGF-like domains (Malinauskas et al, 2011).…”

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confidence: 99%

The WIF domain of the human and Drosophila Wif-1 secreted factors confers specificity for Wnt or Hedgehog

et al. 2012

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There was an error published in Development 139, 3849-3858. Fig. 4B incorrectly showed an image of an apGal4>UAS-hWIF1 wing disc instead of an apGal4>NTDm -WD Hs -EGF Dm wing disc. The correct figure is shown below.As both genotypes display a very similar disc phenotype, this error does not change the conclusions of the paper.The authors apologise to readers for this mistake. CORRIGENDUMThe WIF domain of the human and Drosophila Wif-1 secreted factors confers specificity for Wnt or Hedgehog David Sánchez-Hernández, Javier Sierra, João Ramalho Ortigão-Farias and Isabel Guerrero RESEARCH ARTICLE 3849 Development 139, 3849-3858 (2012) INTRODUCTIONSecreted signaling proteins of the Wnt and Hedgehog (Hh) families have important and conserved roles in metazoan development. These molecules also function postembryonically in homeostatic processes, such as stem cell maintenance. Alterations in these pathways during development cause a variety of congenital disorders and their aberrant activation has been implicated in proliferative disorders leading to many types of human cancer (Logan and Nusse, 2004;Moon et al., 2004). Hh and Wnt signals have been identified as morphogens in various systems. Morphogens are produced from a localized source and spread in the epithelium to form concentration gradients that organize patterning and control growth during development (Tabata and Takei, 2004). The mechanisms of morphogen distribution and the interpretation of morphogen gradients are of fundamental interest.During evolution, organisms have developed many ways to finetune Wnt and Hh signaling. One way of controlling this process is through extracellular modulators that directly interact with Wnt or Hh. It is important to consider how these modulators contribute to the robustness of the gradients and the ability of the cells to measure different morphogen levels. Recently, increasing numbers of cell surface and extracellular modulators have been shown to bind morphogens and to regulate their distribution and signaling. In vertebrates, there are several extracellular modulators of Wnt, including the secreted Frizzled-related protein (SFRP) family (Uren et al., 2000), Cerberus (Willert et al., 2003) and the Wnt inhibitory factor 1 (Wif-1) family (Hsieh et al., 1999).Wif-1 has been described as a secreted antagonist of Wnt signaling (Hsieh et al., 1999;Hunter et al., 2004;Surmann-Schmitt et al., 2009). Hsieh and colleagues have proposed that Wif-1 might sequester Wnt ligands, preventing binding to the receptor Frizzled (Frl) (Hsieh et al., 1999). During development, Wif-1 expression is detectable at early and late stages (Hsieh et al., 1999;Hunter et al., 2004;Surmann-Schmitt et al., 2009). Wif-1 is also expressed in adults in the nervous system, lungs, heart, and cartilage-mesenchyme interfaces of various organisms (Hsieh et al., 1999;Surmann-Schmitt et al., 2009). A relationship between Wif-1 and cancer has also been reported. Thus, human Wif-1 (WIF1) is downregulated in cancers (Mazieres et al., 2004;Kansara et al., 2009) and...

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“…Both OLFM1 and OLFM4 have been implicated in apoptosis. Mutations in OLFM1 [28] and silencing of OLFM1 resulted in increased apoptosis [29]. OLFM4 may have differing roles depending on the tissue, being antiapoptotic in gastric cancers [30] and growth promoting in pancreas and lung cancer cells [31,21].…”

Section: Discussionmentioning

confidence: 99%