Gene expression in regenerating and scarring tails of lizard evidences three main key genes (wnt2b, egfl6, and arhgap28) activated during the regulated process of tail regeneration.
Gene expression
Lizard
Microscopy
Scar
Tail blastema
Journal
Protoplasma
ISSN: 1615-6102
Titre abrégé: Protoplasma
Pays: Austria
ID NLM: 9806853
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
12
06
2020
accepted:
09
08
2020
pubmed:
28
8
2020
medline:
13
8
2021
entrez:
28
8
2020
Statut:
ppublish
Résumé
We have analyzed the expression of key genes orchestrating tail regeneration in lizard under normal and scarring conditions after cauterization. At 1-day post-cauterization (1 dpc), the injured blastema contains degenerating epithelial and mesenchymal cells, numerous mast cells, and immune cells. At 3 and 7 dpc, a stratified wound epidermis is forming while fibrocytes give rise to a scarring connective tissue. Oncogenes such as wnt2b, egfl6, wnt6, and mycn and the tumor suppressor arhgap28 are much more expressed than other oncogenes (hmga2, rhov, fgf8, fgfr4, tert, shh) and tumor suppressors (apcdd1, p63, rb, fat2, bcl11b) in the normal blastema and at 7 dpc. Blastemas at 3 dpc feature the lowest upregulation of most genes, likely derived from damage after cauterization. Immunomodulator genes nfatc4 and lef1 are more expressed at 7 dpc than in normal blastema and 3 dpc suggesting the induction of immune response favoring scarring. Balanced over-expression of oncogenes, tumor suppressor genes, and immune modulator genes determines regulation of cell proliferation (anti-oncogenic), of movement (anti-metastatic), and immunosuppression in the normal blastema. Significant higher expression of oncogenes wnt2b and egfl6 in normal blastema and higher expression of the tumor suppressor arhgap28 in the 7 dpc blastema indicate that they are among the key/master genes that determine the regulated regeneration of the tail.
Identifiants
pubmed: 32852660
doi: 10.1007/s00709-020-01545-6
pii: 10.1007/s00709-020-01545-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3-17Références
Akimoto S, Ishikawa O, IIjima C, Miyachi Y (1999) Expression of basic fibroblast growth factor and its receptors by fibroblasts, macrophages and mast cells in hypertrophic scar. Eur J Dermatol 9:357–362
pubmed: 10417437
Alibardi L (1993) Observations on the ultrastructure of blood capillaries in the regenerating blastema of lizard in relation to the blood-brain barrier. Eur Arch Biol 104(1):21–27
Alibardi L (2010) Morphological and cellular aspects of tail and limb regeneration in lizard: a model system with implications for tissue regeneration in mammals. Adv Anat Embryol Cell Biol 207:1–109
Alibardi L (2013) Ultrastructural observations on the scarring process in the cauterized tail and the amputated limb of lizard. Trends Dev Biol 7:15–24
Alibardi L (2014) Histochemical, biochemical and cell biological aspects of tail regeneration in lizard, an amniote model for studies on tissue regeneration. Progr Histochem Cytochem 48(4):143–244
Alibardi L (2017a) Review: biological and molecular differences between tail regeneration and limb scarring in lizard, an inspiring model addressing limb regeneration in amniotes. J Exp Zool B Mol Dev Evol 328:493–514
pubmed: 28612481
Alibardi L (2017b) Immunolocalization of sonic hedgehog and patched in the regenerating tail of lizard suggests they are involved in cell proliferation and epidermal differentiation. BAOJ Dermatol 1:004
Alibardi L (2018) Perspective: appendages regeneration in amphibians and some reptiles derived from specific evolutionary histories. J Exp Zool 330B:396–405
Alibardi L (2019a) Review. The regenerating tail blastema of lizard as a model to study organ regeneration and tumor growth regulation in amniotes. Anat Rec 302:1469–1490
Alibardi L (2019b) Review. Tail regeneration in lepidosauria as an exception to the generalized lack of organ regeneration in amniotes. J Exp Zool B Mol Dev Evol. https://doi.org/10.1002/jez.b.22901
Alibardi L (2019c) Review. Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes. Histol Histopathol 34:1111–1120
pubmed: 31058307
Andrade P, Pinho C, Pérez I de Lanuza G, Afonso S, Brejcha J, Rubin CJ, Wallerman O, Pereira P, Sabatino SJ, Bellati A, Pellitteri-Rosa D, Bosakova Z, Bunikis I, Carretero MA, Feiner N, Marsik P, Paupério F, Salvi D, Soler L, While GM, Uller T, Font E, Andersson L, Carneiro M (2019) Regulatory changes in pterin and carotenoid genes underlie balanced color polymorphisms in the wall lizard. Proc Natl Acad Sci U S A 116:5633–5642
pubmed: 30819892
pmcid: 6431182
Avram D, Califano D (2014) The multifaceted roles of Bcl11b in thymic and peripheral T cells - impact on immune diseases. J Immunol 193:2059–2065
pubmed: 25128552
pmcid: 4135393
Bai S, Ingram P, Chen YC, Deng N, Pearson A, Niknafs YS, O’Hayer P, Wang Y, Zhang ZY, Boscolo E, Bischoff J, Yoon E, Buckanovich RJ (2016) EGFL6 regulates the asymmetric division, maintenance, and metastasis of ADLH+ ovarian cancer cells. Cancer Res 76:6396–6409
pubmed: 27803106
pmcid: 5120866
Bellairs A d’A, Bryant SV (1985) Autotomy and regeneration in reptiles. In: Gans C, Billet F, Maderson PFA (eds) Biology of the reptilia. Wiley, New York, pp 302–410
Bomben R, Dal-Bo M, Benedetti D, Capello D, Forconi F, Marconi D, Bertoni F, Maffei R, Laurenti L, Rossi D, Del Principe MI, Luciano F, Sozzi E, Cattarossi I, Zucchetto A, Rossi FM, Bulian P, Zucca E, Nicoloso MS, Degan M, Marasca R, Efremov DG, Del PG, Gaidano G, Gattei V (2010) Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features. Clin Cancer Res 16:620–628
pubmed: 20068100
Brandt TM, Iida M, Li C, Wheeler DL (2011) The nuclear epidermal growth factor receptor signaling network. Discov Med 12:419–432
Chen Y, Peng Y, Fan S, Li Y, Xiao ZX, Li C (2018) A double dealing tale of p63: an oncogene or a tumor suppressor. Cell Mol Life Sci 75:965–973
pubmed: 28975366
Cho SG (2017) APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical wnt signaling pathway. Oncol Lett 14:4845–4852
pubmed: 29085490
pmcid: 5649524
Chuong CM, Patel N, Lin J, Jung HS, Widelitz RB (2000) Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution. Cell Mol Life Sci 57:1672–1681
pubmed: 11130174
pmcid: 4381998
Clay MR, Halloran MC (2013) Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition. Development 140:3198–3209
pubmed: 23804498
pmcid: 3931734
Cox PG (1969) Some aspects of tail regeneration in the lizard Anolis carolinensis. II. The role of the peripheral nerves. J Exp Zool 171:151–160
El-Sayed Y (2016) Time course of histomorphologic features during chronic burn wound healing. Forensic Med Anat Res 4:1–6
Fedele M, Battista S, Manfioletti G, Croce CM, Giancotti V, Fusco A (2001) Role of the high mobility group A proteins in human lipomas. Carcinogenesis 22:1583–1591
pubmed: 11576996
Fior J (2014) Salamander regeneration as a model for developing novel regenerative and anticancer therapies. J Cancer 5:715–719
pubmed: 25258653
pmcid: 4174516
Fisher RE, Geiger LA, Stroik LK, Hutchins ED, George RM, DeNardo DF, Kosumi K, Rawls JA, Wilson-Rawls J (2012) A histological comparison of the original and regenerated tail in the green anole, Anolis carolinensis. Anat Rec 295:1609–1619
Geetha-Loganathan P, Nimmagadda S, Scaal M (2008) Wnt signaling in limb organogenesis. Organogenesis 4:109–115
pubmed: 19279722
pmcid: 2634256
Gilbert EA, Delorme SL, Vickaryous MK (2015) The regeneration blastema of lizards: an amniote model for the study on appendage replacement. Regeneration 2:45–53
pubmed: 27499867
pmcid: 4895314
Hutchins ED, Markov GJ, Eckalbar WL, George RM, King JM, Tokuyama MA, Geiger LA, Emmert N, Ammar MJ, Allen AN, Siniard AL, Corneveaux JJ, Fisher RE, Wade J, DeNardo DF, Rawls JA, Huentelman MJ, Wilson-Rawls J, Kusumi K (2014) Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms. PLoS One 9:e105004
pubmed: 25140675
pmcid: 4139331
Katoh M, Katoh M (2009) Transcriptional regulation of wnt2b based on the balance of Hedgehog, Notch, BMP and WNT signals. Int J Oncol 34:1411–1415
pubmed: 19360354
Kawakami Y, Capdevila J, Büscher D, Itoh T, Rodríguez Esteban C, Izpisúa Belmonte JC (2001) Wnt signals control FGF-dependent limb initiation and AER induction in the chick embryo. Cell 104:891–900
pubmed: 11290326
Kominami R (2012) Role of the transcription factor Bcl11b in development of lymphoangiogenesis. Proc Jpn Acad Ser B Phys Biol Sci 88:72–87
pubmed: 22450536
pmcid: 3365246
Lateef Z, Stuart G, Jones N, Mercer A, Fleming S, Wise L (2019) The cutaneous inflammatory response to thermal burn injury in a murine model. Int J Mol Sci 20:E538
pubmed: 30696002
Liu Y, Zhou Q, Wang Y, Luo L, Yang J, Yang L, Liu M, Li Y, Qian T, Zheng Y, Li M, Li J, Gu Y, Han Z, Xu M, Wang Y, Zhu C, Yu B, Yang Y, Ding F, Jiang J, Yang HGX (2015) Gekko japonicus genome reveal evolution of adhesive toe pads and tail regeneration. Nat Commun 6:10033
pubmed: 26598231
pmcid: 4673495
Lozito TP, Tuan RS (2016) Lizard tail skeletal regeneration combines aspects of fracture healing and blastema-based regeneration. Development 143:2946–2957
pubmed: 27387871
pmcid: 5004880
Lozito TP, Tuan RS (2017) Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote. Connect Tissue Res 58:145–154
pubmed: 27459585
Macian F (2005) Nfat proteins: key regulators of T-cell development and function. Nat Rev Immunol 5:472–484
pubmed: 15928679
Marics I, Padilla F, Guillemot JF, Scaal M, Marcelle C (2002) FGFR4 signaling is a necessary step in limb muscle differentiation. Development 129:4559–4569
pubmed: 12223412
Marsch SK, Bansal GS, Zammit C, Barnard R, Coope R, Roberts-Clarke D, Gomm JJ, Coombes RC, Johnston CL (1999) Increased expression of fibroblast growth factor 8 in human breast cancer. Oncogene 18:1053–1060
Mescher AL (2017) Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration. Regeneration 4:39–53
pubmed: 28616244
pmcid: 5469729
Moritz AR (1947) Studies on thermal injury. III. The pathology and pathogenesis of cutaneous burns, an experimental study. Am J Pathol 23:915–941
pubmed: 19970971
pmcid: 1934331
Morris LG, Ramaswami D, Chan TA (2013) The FAT epidemic, a gene family frequently mutated across multiple cancer types. Cell Cycle 12:1011–1012
pubmed: 23493187
pmcid: 3646852
Payne SL, Peacock HM, Vickaryous MK (2017) Blood vessel formation during tail regeneration in the leopard gecko (Eublepharis macularius). J Morphol 278:380–389
pubmed: 28078708
Pomeranz JH, Blau HM (2013) Tumor suppressors: enhancers or suppressors of regeneration? Development 140:2502–2512
Prehn RT (1997) Commentary. Regeneration versus neoplastic growth. Carcinogenesis 18:1439–1444
pubmed: 9276613
Ronca R, Tamma R, Coltrini D, Ruggieri S, Presta M, Ribatti D (2017) Fibroblast growth factor modulates mast cell recruitment in a murine model of prostate cancer. Oncotarget 8:82583–82592
pubmed: 29137286
pmcid: 5669912
Santiago L, Daniels G, Wang D, Deng FM, Lee P (2017) Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment. Am J Cancer Res 7:1389–1406
pubmed: 28670499
pmcid: 5489786
Sarig R, Tzahor E (2017) The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians? Carcinogenesis 38:359–366
pubmed: 28334384
Scala C, Cenacchi G, Ferrari C, Pasquinelli G, Preda P, Manara GC (1992) A new acrylic resin formulation: a useful tool for histological, ultrastructural, and immunocytochemical investigations. J Histochem Cytochem 40:1799–1804
pubmed: 1431065
Schaale K, Brandenburg J, Kispert A, Leitges M, Ehlers S, Reiling N (2013) Wnt6 is expressed in granulomatous lesions of Mycobacterium tuberculosis-infected mice and is involved in macrophage differentiation and proliferation. J Immunol 191:5182–5195
pubmed: 24123681
Shou J, Jing J, Xie J, You L, Jing Z, Yao J, Han W, Pan H (2015) Nuclear factor of activated T cells in cancer development and treatment. Cancer Lett 361:174–184
pubmed: 25766658
Simpson SB (1965) Regeneration of the lizard tail. In: Kiortsis V, Trampusch HAL (eds) Regeneration in animals and related problems. North-Holland, Amsterdam, 431–443
Solis GP, Lüchtenborg AM, Katanaev VL (2013) Wnt secretion and gradient formation. Int J Mol Sci 14:5130–5145
pubmed: 23455472
pmcid: 3634490
Sun X, Mariani FV, Martin GR (2002) Functions of FGF signaling from the apical ectodermal ridge in limb development. Nature 418:501–508
pubmed: 12152071
Thies HW, Nolte I, Wenk H, Mertens F, Bullerdiek J, Markowski DN (2014) Permanent activation of HMGA2 in lipomas mimics its temporal physiological activation linked to the gain of adipose tissue. Obesity 21:141–150
van Helden SF, Anthony EC, Dee R, Hordijk PL (2012) Rho GTPase expression in human myeloid cells. PLoS One 7:e42563
pubmed: 22916134
pmcid: 3420873
Varjosalo M, Taipale J (2008) Hedgehog: functions and mechanisms. Genes Dev 22:2454–2472
pubmed: 18794343
Vélez-Cruz R, Johnson DG (2017) The retinoblastoma (RB) tumor suppressor. Pushing back against genome instability on multiple fronts. Int J Mol Sci 18:E1776
pubmed: 28812991
Vitulo N, Dalla Valle L, Skobo T, Valle G, Alibardi L (2017a) Transcriptome analysis of the regenerating tail versus the scarring limb in lizard reveals pathways leading to successful versus unsuccessful organ regeneration in amniotes. Dev Dyn 246:116–134
pubmed: 27870483
Vitulo N, Dalla Valle L, Skobo T, Valle G, Alibardi L (2017b) Down-regulation of lizard immuno-genes in the regenerating tail and myo-genes in the scarring limb suggests that tail regeneration occurs in an immuno-privileged organ. Protoplasma 254:2127–2141
pubmed: 28357509
Whyte JL, Smith AA, Helms JA (2016) Wnt signaling and injury repair. Cold Spring Harb Perspect Biol 4:a008078
Wilgus TA, Wulff BC (2014) The importance of mast cells in dermal scarring. Adv Wound Care 3:356–365
Wulff BC, Parent AE, Meleski MA, DiPietro LA, Schrementi ME, Wilgus TA (2012) Mast cells contribute to scar formation during fetal wound healing. J Inv Dermatol 132:458–465
Xing S, Gai K, Li X, Shao P, Zeng Z, Zhao X, Zhao X, Chen X, Paradee WJ, Meyrholz DK, Peng W, Xue HH (2019) Tcf1 and Lef1 are required for the immunosuppressive function of regulatory T cells. J Exp Med 216:847–866
pubmed: 30837262
pmcid: 6446865
Yeung CYC, Taylor SH, Garva R, Holmes DF, Zeef LA, Soininen R, Booth-Handford RP, Kadler KE (2014) Arggap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers. PLoS One 9:e107036
pubmed: 25211221
pmcid: 4161385