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However, WDR11's role in development is poorly understood. Here, we report that WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for ciliogenesis. Disruption of WDR11 expression in mouse and zebrafish results in phenotypic characteristics associated with defective Hh signalling, accompanied by dysgenesis of ciliated tissues.\n                    <jats:italic>Wdr11<\/jats:italic>\n                    \u2010null mice also exhibit early\u2010onset obesity. We find that WDR11 shuttles from the cilium to the nucleus in response to Hh signalling. WDR11 regulates the proteolytic processing of GLI3 and cooperates with the transcription factor EMX1 in the induction of downstream Hh pathway gene expression and gonadotrophin\u2010releasing hormone production. The CHH\/KS\u2010associated human mutations result in loss of function of WDR11. Treatment with the Hh agonist purmorphamine partially rescues the WDR11 haploinsufficiency phenotypes. Our study reveals a novel class of ciliopathy caused by WDR11 mutations and suggests that CHH\/KS may be a part of the human ciliopathy spectrum.\n                  <\/jats:p>","DOI":"10.15252\/embr.201744632","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T20:10:42Z","timestamp":1513800642000},"page":"269-289","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["WDR11\u2010mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome"],"prefix":"10.1038","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8896-1153","authenticated-orcid":false,"given":"Yeon\u2010Joo","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel PS","family":"Osborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatake","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Mohun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"K\u00e4ns\u00e4koski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Brandstack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Taek","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3069-2725","authenticated-orcid":false,"given":"Francesc","family":"Miralles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol\u2010Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel A","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung\u2010Goo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pedro","family":"Martinez\u2010Barbera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paris","family":"Ataliotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taneli","family":"Raivio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence C","family":"Layman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-1437","authenticated-orcid":false,"given":"Soo\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"BFEMBR201744632_CR1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.gde.2009.04.008","volume":"19","author":"MA Lancaster","year":"2009","unstructured":"Lancaster MA, Gleeson JG (2009) The primary cilium as a cellular signaling center: lessons from disease. 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