{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:19:39Z","timestamp":1788589179641,"version":"build-2803163510"},"reference-count":120,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100004184","name":"Northeastern University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004184","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1558017"],"award-info":[{"award-number":["1558017"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000183","name":"Army Research Office","doi-asserted-by":"publisher","award":["56157-LS-MUR"],"award-info":[{"award-number":["56157-LS-MUR"]}],"id":[{"id":"10.13039\/100000183","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,15]]},"abstract":"<jats:p>Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RAR\u03b3 agonist) or truncate (RAR\u03b2 antagonist) regenerating limbs. RARE-EGFP reporter axolotls showed divergent reporter activity in limbs undergoing PD duplication versus truncation, suggesting differences in patterning and skeletal regeneration. Transcriptomics identified expression patterns that explain PD duplication, including upregulation of proximal homeobox gene expression and silencing of distal-associated genes, whereas limb truncation was associated with disrupted skeletal differentiation. RAR\u03b2 antagonism in uninjured limbs induced a loss of skeletal integrity leading to long bone regression and loss of skeletal turnover. Overall, mechanisms were identified that regulate the multifaceted roles of RARs in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.<\/jats:p>","DOI":"10.1242\/dev.139873","type":"journal-article","created":{"date-parts":[[2017,1,14]],"date-time":"2017-01-14T02:20:25Z","timestamp":1484360425000},"page":"601-611","source":"Crossref","is-referenced-by-count":30,"title":["Retinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl"],"prefix":"10.1242","volume":"144","author":[{"given":"Matthew","family":"Nguyen","sequence":"first","affiliation":[{"name":"Northeastern University 1 Department of Biology , , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankhuri","family":"Singhal","sequence":"additional","affiliation":[{"name":"Northeastern University 1 Department of Biology , , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith W.","family":"Piet","sequence":"additional","affiliation":[{"name":"Northeastern University 2 Mechanical and Industrial Engineering , , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"Shefelbine","sequence":"additional","affiliation":[{"name":"Northeastern University 2 Mechanical and Industrial Engineering , , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-5309","authenticated-orcid":false,"given":"Malcolm","family":"Maden","sequence":"additional","affiliation":[{"name":"UF Genetics Institute, University of Florida 3 Department of Biology and \u2008 , Gainesville, FL 32611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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