{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:59:52Z","timestamp":1781323192103,"version":"3.54.1"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We know little about the control of positional information (PI) during axolotl limb regeneration, which ensures that the limb regenerates exactly what was amputated, and the work reported here investigates this phenomenon. Retinoic acid administration changes the PI in a proximal direction so that a complete limb can be regenerated from a hand. Rather than identifying all the genes altered by RA treatment of the limb, we have eliminated many off-target effects by using retinoic acid receptor selective agonists. We firstly identify the receptor involved in this respecification process as RAR\u03b1 and secondly, identify the genes involved by RNA sequencing of the RAR\u03b1-treated blastemal mesenchyme. We find 1177 upregulated genes and 1403 downregulated genes, which could be identified using the axolotl genome. These include several genes known to be involved in retinoic acid metabolism and in patterning. Since positional information is thought to be a property of the cell surface of blastemal cells when we examine our dataset with an emphasis on this aspect, we find the top canonical pathway is integrin signaling. In the extracellular matrix compartment, we find a MMP and several collagens are upregulated; several cell membrane genes and secretory factors are also upregulated. This provides data for future testing of the function of these candidates in the control of PI during limb regeneration.<\/jats:p>","DOI":"10.3390\/cells10092174","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"2174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Retinoic Acid Receptors and the Control of Positional Information in the Regenerating Axolotl Limb"],"prefix":"10.3390","volume":"10","author":[{"given":"Trey","family":"Polvadore","sequence":"first","affiliation":[{"name":"Department of Biology & UF Genetics Institute, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Maden","sequence":"additional","affiliation":[{"name":"Department of Biology & UF Genetics Institute, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1242\/dev.102.4.687","article-title":"Retinoic acid coordinately proximalizes regenerate pattern and blastema differential affinity in axolotl limbs","volume":"102","author":"Crawford","year":"1988","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/273232a0","article-title":"Supernumerary limbs in the axolotl","volume":"237","author":"Maden","year":"1978","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1432-0436.1984.tb01334.x","article-title":"Surface properties of regenerating limb cells: Evidence for gradation along the proximodistal axis","volume":"25","author":"Nardi","year":"1983","journal-title":"Differentiation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/295672a0","article-title":"Vitamin A and pattern formation in the regenerating limb","volume":"295","author":"Maden","year":"1982","journal-title":"Nature"},{"key":"ref_5","first-page":"273","article-title":"The effect of vitamin A on the regenerating amphibian limb","volume":"77","author":"Maden","year":"1983","journal-title":"J. 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