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Following tail amputation, inflammation is low and cell proliferation high, leading to regeneration while the intense inflammation in the limb leads to low proliferation and scarring. FGFs stimulate tail and limb regeneration and are present in the wound epidermis and blastema while they disappear in the limb wound epidermis 2\u20133 weeks postamputation in the scarring outgrowth. FGFs localize in the tail blastema and the apical epidermal peg (AEP), an epidermal microregion that allows tail growth but is absent in the limb. Inflammatory cells invade the limb blastema and wound epidermis, impeding the formation of an AEP. An embryonic program of growth is activated in the tail, dominated by Wnt\u2010positive and \u2010negative regulators of cell proliferation and noncoding RNAs, that represent the key regenerative genes. The balanced actions of these regulators likely impede the formation of a tumor in the tail tip. Genes for FACIT and fibrillar collagens, protease inhibitors, and embryonic keratins are upregulated in the regenerating tail blastema. A strong downregulation of genes for both B and T\u2010lymphocyte activation suggests the regenerating tail blastema is a temporal immune\u2010tolerated organ, whereas a scarring program is activated in the limb. Wnt inhibitors, pro\u2010inflammatory genes, negative regulators of cell proliferation, downregulation of myogenic genes, proteases, and oxidases favoring scarring are upregulated. The evolution of an efficient immune system may be the main limiting barrier for organ regeneration in amniotes, and the poor regeneration of mammals and birds is associated with the efficiency of their mature immune system. This does not tolerate embryonic antigens formed in reprogrammed embryonic cells (as for neoplastic cells) that are consequently eliminated impeding the regeneration of lost organs.<\/jats:p>","DOI":"10.1002\/jez.b.22754","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T01:26:44Z","timestamp":1497403604000},"page":"493-514","source":"Crossref","is-referenced-by-count":54,"title":["Review: Biological and Molecular Differences between Tail Regeneration and Limb Scarring in Lizard: An Inspiring Model Addressing Limb Regeneration in Amniotes"],"prefix":"10.1002","volume":"328","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-2217","authenticated-orcid":false,"given":"Lorenzo","family":"Alibardi","sequence":"first","affiliation":[{"name":"Comparative Histolab and Department of Biology University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,14]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"AdzickNS LongakerMT.1992.Fetal wound healing.New York:Elsevier."},{"key":"e_1_2_11_3_1","first-page":"55","article-title":"Fenomeni degenerativi nell' ependima durante la rigenerazione codale di alcuni sauri (Degenerating process in the ependyma during tail regeneration in saurians)","volume":"98","author":"Alibardi L","year":"1986","journal-title":"Atti Mem Acc Patav Sci Lett Arti"},{"key":"e_1_2_11_4_1","first-page":"119","article-title":"Fine autoradiographical study on scale morphogenesis in the regenerating tail of lizards","volume":"9","author":"Alibardi L","year":"1994","journal-title":"Histol Histopathol"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-03733-7_1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1463-6395.2009.00409.x","article-title":"Ultrastructural features of the process of wound healing after tail and limb amputation in lizard","volume":"9","author":"Alibardi L","year":"2010","journal-title":"Acta Zool"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.26496\/bjz.2012.134","article-title":"Observations on FGFs immunoreactivity in the regenerating tail blastema and in the limb and tail scars of lizard suggest that FGFs are required for regeneration","volume":"142","author":"Alibardi L","year":"2012","journal-title":"Belg J Zool"},{"key":"e_1_2_11_8_1","first-page":"15","article-title":"Ultrastructural observations on the scarring process in the cauterized tail and the amputated limb of lizard","volume":"7","author":"Alibardi L","year":"2013","journal-title":"Trends Dev Biol"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.proghi.2013.12.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.22581"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.20375"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","unstructured":"AlibardiL.2015c.Immunolocalization of a p53\/p63\u2010like protein in the regenerating tail epidermis of the wall lizard (Podarcis muralis) suggests it is involved in the differentiation of the epidermis. 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