Immunolocalization of tumor suppressors arhgap28 and retinoblastoma in the lizard Podarcis muralis suggests that they contribute to the regulated regeneration of the tail

Abstract

Tail regeneration in lizards is an outstanding and unique postembryonic morphogenetic process. This developmental process is regulated by poorly known factors, but recent studies have suggested that it derives from a balanced activity between oncoproteins and tumor suppressors. Transcriptome and expression data have

The regenerating tail of lizard transits through a tumour‐like stage represented by the regenerative blastema

“…The transcriptome and some expression studies conducted on the regenerating blastema-cones of P. muralis have found that among the main oncogenes exclusively activated in the tail, but not in the limb, are 5-6 members of the Wnt and FGF/EGF pathways and a number of noncoding RNAs (snora e scarna; Vitulo et al, 2017a). The main 4 ncRNAs detected in the tail blastema, snord63, snord74, scarna11 are up-regulated in various tumours and only snord26 may function as tumour suppressor (Alibardi, 2019a(Alibardi, , 2022Vitulo et al, 2017a). C-myc and telomerase are also activated in some cells a few days after tail amputation (Figure 2k).…”

“…The observation that a regenerating blastema rapidly elongates into a differentiated tail and not into a tumorigenic outgrowth has further indicated that strict and efficient mechanisms of control in cell proliferation are present in lizard tissues. Therefore, it has been proposed that the growth of the lizard blastema is regulated by the balanced action of oncogenes and tumour suppressors, a mechanism that may have evolved only in lizards among terrestrial vertebrates (Alibardi, 2021a(Alibardi, , 2022.…”

“…A further difference with malignant tumours or cancers is the lack of metastatization of blastema cells that do not migrate through the blood into other regions of the body. It has been hypothesized that only the more distal cells in a conical blastema that are close and/or contacting the wound epidermis, do not undergo 'contact inhibition' while those in contact/close to the normal tissues of the stump are induced to differentiate, impeding metastatization (Alibardi, 2019a(Alibardi, , 2022; Figure 2i). Numerous tumoursuppressors (apc, rb, aghgap28, dkk3 etc.)…”

“…A common observation is that the two main tissues leading to the regeneration of a new tail, the apical wound epidermis and the ependymal tube, a simple continuation of the original spinal cord (Figure1j), immunolocalize both onco‐genes and tumour suppressor proteins (Alibardi, 2017a, 2019a, 2019b, 2021a, 2022). This indicates that a tight control on cell proliferation–inhibition is very active in these key tissues that control the regeneration of the tail in lizard.…”

“…These cells contain a diffuse cytoskeleton and some bundles sustaining the thicker elongations, and they are labelled for actin and also for keratin 17 and 16 (Alibardi & Polazzi, 2012). During this process cells collected from the entire blastema‐cone initially dedifferentiate in vitro forming mesenchymal‐like cells of irregular shape, rich in actin and featuring a relatively simple ultrastructure and express some markers such as nestin, vimentin and the dynamic‐elastic keratins 17 (Alibardi, 2021a; Alibardi, 2022; Alibardi & Polazzi, 2012; Polazzi & Alibardi, 2011).…”