{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:17:04Z","timestamp":1784675824858,"version":"3.55.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["no. 1037\/15 (to D.S. and B.M.)"],"award-info":[{"award-number":["no. 1037\/15 (to D.S. and B.M.)"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["no. 368\/19 (to B.M.)"],"award-info":[{"award-number":["no. 368\/19 (to B.M.)"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001742","name":"United States-Israel Binational Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Dehydrodolichyl diphosphate synthase (DHDDS) is a ubiquitously expressed enzyme that catalyzes <jats:italic>cis<\/jats:italic>-prenyl chain elongation to produce the poly-prenyl backbone of dolichol. It appears in all tissues including the nervous system and it is a highly conserved enzyme that can be found in all animal species. Individuals who have biallelic missense mutations in the <jats:italic>DHDDS<\/jats:italic> gene are presented with non-syndromic retinitis pigmentosa with unknown underlying mechanism. We have used the <jats:italic>Drosophila<\/jats:italic> model to compromise <jats:italic>DHDDS<\/jats:italic> ortholog gene (<jats:italic>CG10778<\/jats:italic>) in order to look for cellular and molecular mechanisms that, when defective, might be responsible for this retinal disease. The Gal4\/UAS system was used to suppress the expression of <jats:italic>CG10778<\/jats:italic> via RNAi-mediated-knockdown in various tissues. The resulting phenotypes were assessed using q-RT-PCR, transmission-electron-microscopy (TEM), electroretinogram, antibody staining and Western blot analysis. Targeted knockdown of <jats:italic>CG10778<\/jats:italic>-mRNA in the early embryo using the actin promoter or in the developing wings using the <jats:italic>nub<\/jats:italic> promoter resulted in lethality, or wings loss, respectively. Targeted expression of <jats:italic>CG10778<\/jats:italic>-RNAi using the <jats:italic>glass multiple reporter<\/jats:italic> (GMR)-Gal4 driver (GMR-DHDDS-RNAi) in the larva eye disc and pupal retina resulted in a complex phenotype: (a) TEM retinal sections revealed a unique pattern of retinal-degeneration, where photoreceptors R2 and R5 exhibited a nearly normal structure of their signaling-compartment (rhabdomere), but only at the region of the nucleus, while all other photoreceptors showed retinal degeneration at all regions. (b) Western blot analysis revealed a drastic reduction in rhodopsin levels in GMR-DHDDS-RNAi-flies and TEM sections showed an abnormal accumulation of endoplasmic reticulum (ER). To conclude, compromising DHDDS in the developing retina, while allowing formation of the retina, resulted in a unique pattern of retinal degeneration, characterized by a dramatic reduction in rhodopsin protein level and an abnormal accumulation of ER membranes in the photoreceptors cells, thus indicating that DHDDS is essential for normal retinal formation.<\/jats:p>","DOI":"10.3389\/fnmol.2021.693967","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T04:57:00Z","timestamp":1625461020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Knockdown of Dehydrodolichyl Diphosphate Synthase in the Drosophila Retina Leads to a Unique Pattern of Retinal Degeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Tal","family":"Brandwine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reut","family":"Ifrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzofia","family":"Bialistoky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Zaguri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisheva","family":"Rhodes-Mordov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Mizrahi-Meissonnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dror","family":"Sharon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir L.","family":"Katanaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Offer","family":"Gerlitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baruch","family":"Minke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4886","DOI":"10.1002\/j.1460-2075.1994.tb06816.x","article-title":"The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin.","volume":"13","author":"Baker","year":"1994","journal-title":"EMBO J."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18970-z","article-title":"Structural basis of heterotetrameric assembly and disease mutations in the human cis-prenyltransferase complex.","volume":"11","author":"Bar-El","year":"2020","journal-title":"Nat. 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