{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:54Z","timestamp":1753891614550,"version":"3.41.2"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Although mutations in <jats:italic>ADAMTS10<\/jats:italic> have long been known to cause autosomal recessive Weill-Marchesani Syndrome which is characterized by short stature and ocular abnormalities, more recent work has shown that certain mutations in <jats:italic>ADAMTS10<\/jats:italic> cause glaucoma in dogs. In humans, glaucoma is the leading cause of irreversible vision loss that affects tens of millions of people world-wide. Vision loss in glaucoma is a result of neurodegeneration of retinal ganglion cells that form the inner-most layer of the retina and whose axons form the optic nerve which relays visual information to the brain. ADAMTS10 contributes to the formation of microfibrils which sequester latent transforming growth factor <jats:italic>\u03b2<\/jats:italic> (TGF\u03b2). Among its many biological functions, TGF\u03b2 promotes the development of retinal ganglion cells and is also known to play other roles in glaucoma pathogenesis. The aim of this study was to test the hypothesis that ADAMTS10 plays a role in retinal ganglion cell development through regulation of TGF\u03b2 signaling. To this end, Adamts10 expression was targeted for reduction in zebrafish embryos carrying either a fluorescent reporter that labels retinal ganglion cells, or a fluorescent reporter of pSmad3-mediated TGF\u03b2 family signaling. Loss of adamts10 function in zebrafish embryos reduced retinal ganglion cell reporter fluorescence and prevented formation of an ordered retinal ganglion cell layer. Targeting adamts10 expression also drastically reduced constitutive TGF\u03b2 signaling in the eye. Direct inhibition of the TGF\u03b2 receptor reduced retinal ganglion cell reporter fluorescence similar to the effect of targeting adamts10 expression. These findings unveil a previously unknown role for Adamts10 in retinal ganglion cell development and suggest that the developmental role of Adamts10 is mediated by active TGF\u03b2 family signaling. In addition, our results show for the first time that Adamts10 is necessary for pSmad3-mediated constitutive TGF\u03b2 family signaling.<\/jats:p>","DOI":"10.3389\/fmolb.2022.989851","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T07:51:45Z","timestamp":1662450705000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Adamts10 controls transforming growth factor \u03b2 family signaling that contributes to retinal ganglion cell development"],"prefix":"10.3389","volume":"9","author":[{"given":"Lauren K.","family":"Wareham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy E.","family":"Whitener","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang-Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Yu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassane S.","family":"Mchaourab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas P.","family":"Mortlock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel W.","family":"Kuchtey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kuchtey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e111941","DOI":"10.1371\/journal.pone.0111941","article-title":"A novel missense mutation in adamts10 in norwegian elkhound primary glaucoma","volume":"9","author":"Ahonen","year":"2014","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.cub.2005.01.014","article-title":"Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus","volume":"15","author":"Aizawa","year":"2005","journal-title":"Curr. 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