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Accordingly in mice,\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    appears adequate for development,\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    functional knockouts (KOs),\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved\n                    <jats:italic>\n                      <jats:underline>L<\/jats:underline>\n                    <\/jats:italic>\n                    <jats:italic>mx1b<\/jats:italic>\n                    -\n                    <jats:underline>a<\/jats:underline>\n                    ssociated\n                    <jats:italic>cis<\/jats:italic>\n                    -\n                    <jats:underline>r<\/jats:underline>\n                    egulatory\n                    <jats:underline>m<\/jats:underline>\n                    odules (\n                    <jats:italic>LARM1<\/jats:italic>\n                    and\n                    <jats:italic>LARM2)<\/jats:italic>\n                    that are bound by Lmx1b, amplify\n                    <jats:italic>Lmx1b<\/jats:italic>\n                    expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal\n                    <jats:italic>LMX1B<\/jats:italic>\n                    coding sequence, but with loss-of-function variations in the\n                    <jats:italic>LARM1\/2<\/jats:italic>\n                    region, stressing the role of regulatory modules in disease pathogenesis.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-25844-5","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T06:02:53Z","timestamp":1632117773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0229-6365","authenticated-orcid":false,"given":"Endika","family":"Haro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-1023","authenticated-orcid":false,"given":"Florence","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmaine U.","family":"Pira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor D.","family":"Spady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lucas-Toca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren I.","family":"Yorozuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-9423","authenticated-orcid":false,"given":"Austin L.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Escande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Jourdain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-9212","authenticated-orcid":false,"given":"Andy","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-4768","authenticated-orcid":false,"given":"Florence","family":"Fellmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-7597","authenticated-orcid":false,"given":"Jean-Marc","family":"Good","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Francannet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8837-3386","authenticated-orcid":false,"given":"Sylvie","family":"Manouvrier-Hanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-7671","authenticated-orcid":false,"given":"Marian A.","family":"Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-4273","authenticated-orcid":false,"given":"Kerby C.","family":"Oberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"key":"25844_CR1","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/0092-8674(95)90103-5","volume":"83","author":"RD Riddle","year":"1995","unstructured":"Riddle, R. 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