{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:52:47Z","timestamp":1790819567298,"version":"4.1.0"},"reference-count":110,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","award":["A-grant"],"award-info":[{"award-number":["A-grant"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R01GM113023"],"award-info":[{"award-number":["1R01GM113023"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The role of compartmentalized signaling in primary cilia during tissue morphogenesis is not well understood. The cilia localized G protein-coupled receptor, Gpr161, represses hedgehog pathway via cAMP signaling. We engineered a knock-in at the\n                    <jats:italic>Gpr161<\/jats:italic>\n                    locus in mice to generate a variant (Gpr161\n                    <jats:sup>mut1<\/jats:sup>\n                    ), which was ciliary localization defective but cAMP signaling competent. Tissue phenotypes from hedgehog signaling depend on downstream bifunctional Gli transcriptional factors functioning as activators or repressors. Compared to knockout (ko),\n                    <jats:italic>\n                      Gpr161\n                      <jats:sup>mut1\/ko<\/jats:sup>\n                    <\/jats:italic>\n                    had delayed embryonic lethality, moderately increased hedgehog targets, and partially down-regulated Gli3 repressor. Unlike ko, the\n                    <jats:italic>\n                      Gpr161\n                      <jats:sup>mut1\/<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>ko<\/jats:sup>\n                    neural tube did not show Gli2 activator-dependent expansion of ventral-most progenitors. Instead, the intermediate neural tube showed progenitor expansion that depends on loss of Gli3 repressor. Increased extraciliary receptor levels in\n                    <jats:italic>\n                      Gpr161\n                      <jats:sup>mut1\/mut1<\/jats:sup>\n                    <\/jats:italic>\n                    prevented ventralization. Morphogenesis in limb buds and midface requires Gli repressor; these tissues in\n                    <jats:italic>\n                      Gpr161\n                      <jats:sup>mut1\/mut1<\/jats:sup>\n                    <\/jats:italic>\n                    manifested hedgehog hyperactivation phenotypes\u2014polydactyly and midfacial widening. Thus, ciliary and extraciliary Gpr161 pools likely establish tissue-specific Gli repressor thresholds in determining morpho-phenotypic outcomes.\n                  <\/jats:p>","DOI":"10.7554\/elife.67121","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T08:00:47Z","timestamp":1628064047000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67121","source":"Crossref","is-referenced-by-count":32,"title":["Ciliary and extraciliary Gpr161 pools repress hedgehog signaling in a tissue-specific manner"],"prefix":"10.7554","volume":"10","author":[{"given":"Sun-Hee","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandarigoda N","family":"Somatilaka","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"White","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4790-3090","authenticated-orcid":true,"given":"Saikat","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","article-title":"Cellular signalling by primary cilia in development, organ function and disease","volume":"15","author":"Anvarian","year":"2019","journal-title":"Nature Reviews 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