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<title>Loss of NLZ2 Expression Results in Coloboma and Abnormal RPE Development in Mouse | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Loss of NLZ2 Expression Results in Coloboma and Abnormal RPE Development in Mouse</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-17">Thursday, September 17, 2015</time>
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– Poster Session II
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">12:00 – 1:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NEI</strong></p></div><div class="schedule__description"><p><strong>DEVBIO-1</strong></p></div></div></div></div><h2>Authors</h2><ul><li>E Boobalan</li><li>RP Alur</li><li>L Dong</li><li>G Shih</li><li>F Onojafe</li><li>O Memon</li><li>K Bharti</li><li>BP Brooks</li></ul><h2>Abstract</h2><p>Failure of the optic fissure—a transiently open gap in the ventral optic cup during normal eye development—results in uveal coloboma, a cause of childhood blindness. We have previously shown that nlz2 is important for optic fissure closure in zebrafish. Here, we examine the role of Nlz2 in optic fissure closure in a mouse knockout (KO) model. Nlz2 expression was evaluated during eye morphogenesis in wild-type (WT) and Nlz2 KO mice along with Pax2, Pax6, Vsx2, Mitf and Otx2. Nlz2 (-/-) embryos exhibit coloboma and a striking decrement in RPE pigmentation. NLZ2 was dynamically expressed in the optic stalk/vesicle/cup in WT embryos at E10.5, E11.5 and E12.5; KO mice showed no expression. In KO mice, PAX6 expression was abnormally expanded into the optic stalk, while PAX2 expression was expanded in the RPE. Both OTX2 and MITF levels were decreased in the RPE whereas OTX2 levels were increased in the dorsal neural retina. The proximal RPE layer was thickened and positive for VSX2 staining. Western blot shows NLZ2 expression in hfRPE and ARPE-19 cells. Loss of NLZ2 expression leads to coloboma in mice and associated with dysregulation of several key transcription factors. We posit that the hypopigmentation and abnormal morphology of KO embryos RPE is related to the reduced levels of MITF expression. VSX2 staining in the thickened presumptive RPE suggests that these cells may be differentiating along a more neural-retina-path. These data suggest that NLZ2 is critical in mammalian eye development, optic fissure closure and RPE cell differentiation/melanogenesis.</p><p><strong>Scientific Focus Area</strong>: Developmental Biology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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