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Cell adhesion and junctional proteins in the developing skin of snakes indicate they coordinate the differentiation of the epidermis

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Abstract

The development of scales and the sequence of epidermal layers during snake embryogenesis has been studied by immunofluorescence for the localization of cell adhesion, adherens, and communicating cell junctional proteins. At about 2nd/3rd of embryonic development in snakes the epidermis forms symmetric bumps at the beginning of scale formation, and they rapidly become asymmetric and elongate forming outer and inner surfaces of the very overlapped scales seen at hatching. The dermis separates a superficial loose from a deeper dense part; the latter is joined to segmental muscles and nerves, likely acting on scale orientation during snake movements. N-cam is present in the differentiating epidermis and mesenchyme of forming scales while L-cam is only/mainly detected in the periderm and epidermis. Mesenchymal N-cam is associated with the epidermis of the elongating dorsal scale surface and with the beta-differentiation that occurs in the overlapping outer surface of scales. Beta-catenin and Connexin-43 show a similar distribution, and they are mainly present in the periderm and differentiating suprabasal keratinocytes likely forming an intense connectivity during epidermal differentiation. Beta-catenin also shows nuclear localization in differentiating cells of the shedding and beta-layers at late stages of scale morphogenesis, before hatching. The study suggests that intensification of adhesion and gap junctions allows synchronization of the differentiation of suprabasal cells to produce the ordered sequence of epidermal layers of snake scales, starting from the shedding complex and the beta-layer.

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References

  • Alibardi L (1998) Glycogen distribution in relation to epidermal cell differentiation during embryonic scale morphogenesis in the lizard Anolis lineatopus. Acta Zool 79:91–100

    Article  Google Scholar 

  • Alibardi L (2002) Ultrastructure of the embryonic snake skin and putative role of histidine in the differentiation of the shedding complex. J Morphol 251:149–168

    Article  CAS  PubMed  Google Scholar 

  • Alibardi L (2003) Adaptation to the land: the skin of reptiles in comparison to that of amphibians and endotherm amniotes. J Exp Zool 298B:12–41

    Article  CAS  Google Scholar 

  • Alibardi L (2004) Dermo-epidermal interactions in reptilian scales: speculations on the evolution of scales, feathers and hairs. J Exp Zool B 302:365–383

    Article  Google Scholar 

  • Alibardi L (2014a) Transition from embryonic to adult epidermis in reptiles occurs by the production of corneous beta-proteins. Int J Dev Biol 58:829–839

    Article  CAS  PubMed  Google Scholar 

  • Alibardi L (2014b) Formation of adherens and communicating junctions coordinate the differentiation of the shedding-layer and beta-epidermal generation in regenerating lizard epidermis. J Morphol 275:693–702

    Article  CAS  PubMed  Google Scholar 

  • Alibardi L, Thompson MB (2003) Epidermal differentiation during ontogenesis and after hatching in the snake Liasis fuscus (Pythonidae, Serpentes, Reptilia) with emphasis on the formation of the shedding complex. J Morphol 256(256):29–51

    Article  CAS  PubMed  Google Scholar 

  • Alibardi L, Toni M (2006) Cytochemical, biochemical and molecular aspects of the process of keratinization in the epidermis of reptilian scales. Progr Histoch Cytoch 40:73–134

    Article  CAS  Google Scholar 

  • Alibardi L, Minelli D (2016) Sites of cell proliferation during scute morphogenesis in turtle and alligator are different from those of lepidosaurian scales. Acta Zool 97:127–141

    Article  Google Scholar 

  • Arita K, Akiyama M, Tsuji Y, McMillian JR, Eady RAJ, Shimizu H (2002) Changes in gap junction distribution and connexin expression pattern during human fetal skin development. J Histoch Cytochem 50:1493–1500

    Article  CAS  Google Scholar 

  • Chang C, Wu P, Baker RE, Maini PK, Alibardi L, Chuong CM (2009) Reptile scale paradigm. Evo-devo, pattern formation and regeneration. Int J Dev Biol 53:813–826

    Article  PubMed  PubMed Central  Google Scholar 

  • Chuong CM, Edelman GM (1985) Expression of cell adhesion molecules in embryonic induction. I. Morphogenesis of nestling feathers. J Cell Biol 101:1009–1026

    Article  CAS  PubMed  Google Scholar 

  • Clevers H, Loh KM, Nusse R (2014) Review. An integral program for tissue renewal and regeneration: wnt signaling and stem cell control. Science 346(6205):1248012

    Article  PubMed  CAS  Google Scholar 

  • Dhouailly D (1977) Dermo-epidermal interactions during morphogenesis of cutaneous appendages in amniotes. Front Matrix Biol 4:86–121

    CAS  Google Scholar 

  • Dhouailly D, Maderson PFA (1984) Ultrastructural observations on the embryonic development of the integument of Lacerta muralis (Lacertilia, Reptilia). J Morphol 179:203–228

    Article  CAS  PubMed  Google Scholar 

  • Dhouailly D, Godefroit P, Martin T, Nonchev S, Caraguel F, Oftedal O (2017) Getting to the root of scales, feathers, hairs: as deep as odontodes? Exp Dermatol 28:503–508

    Article  PubMed  Google Scholar 

  • Di-Poi N, Milinkovitch MC (2016) The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes. Sci Adv 2:e1600708

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Downing SW, Roth SI (1974) The derivation of the cells of the epidermal strata of the boa constrictor (Constrictor constrictor). J Inv Derm 62:450–457

    Article  CAS  Google Scholar 

  • Dujsebayeva TN (2009) The skin development in the Pallas’ coluber, Elaphe dione (Pallas, 1773) (Serpentes, Colubridae). Russ J Herpethol 15:44–54

    Google Scholar 

  • Flaxman BA, Maderson PFA (1973) Relationship between pattern of cell migration from the germinal layer and changing pattern of differentiation in the lizard epidermis. J Exp Zool 183:209–216

    Article  CAS  PubMed  Google Scholar 

  • Goliger JA, Paul DL (1994) Expression of gap junction proteins Cx26, Cx31.1, Cx37, and Cx43 in developing and mature rat dermis. Dev Dyn 200:1–13

    Article  CAS  PubMed  Google Scholar 

  • Halbleib JM, Nelson JW (2006) Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev 20:3199–3214

  • Hardy MH, Vielkind U (1996) Changing patterns of cell adhesion molecules during mouse pelage hair follicle development. Acta Anat 157:168–182

    Article  Google Scholar 

  • Holthaus KB, Eckhart L, Dalla Valle L, Alibardi L (2019) Review: evolution and diversification of corneous beta-proteins, the characteristic epidermal proteins of reptiles and birds. J Exp Zool 330B:438–453

    Google Scholar 

  • Kaplan ED, Holbrook KA (1994) Dynamic pattern expression of tenascin, proteoglycans, and cell adhesion molecules during human hair follicle morphogenesis. Dev Dyn 199:141–155

    Article  CAS  PubMed  Google Scholar 

  • Klein MCG, Deuschle JK, Gorb SN (2010) Material properties of the skin of the Kenyan sand boa Gongylophis colubrinus (Squamata, Boidae). J Comp Physiol 196A:659–668

    Article  Google Scholar 

  • Jiang TX, Chuong MC (1992) Mechanism of skin morphogenesis. I. Analyses with antibodies to adhesion molecules tenascin. N-Cam and Integrin Dev Biol 150:82–98

    CAS  PubMed  Google Scholar 

  • Landmann L (1979) Keratin formation and barrier mechanisms in the epidermis of Natrix natrix (Reptilia, Serpentes): an ultrastructural study. J Morphol 162:93–126

    Article  PubMed  Google Scholar 

  • Landmann L (1980) Zonulae occludentes in the epidermis of the snake Natrix natrix L. Experientia 36:110–112

    Article  CAS  PubMed  Google Scholar 

  • Landmann L (1986) The skin of reptiles. Epidermis and dermis. In: Bereiter-Hahn J, Matoltsy AG, Sylvia-Richards K (eds) Biology of the integument, vol 2Vertebrates. Springer-Verlag, Berlin and New York, pp 150–187

    Chapter  Google Scholar 

  • Landmann L, Stolinski C, Martin B (1981) The permeability barrier in the epidermis of the grass snake during the resting stage of the sloughing cycle. Cell Tiss Res 215:369–382

    Article  CAS  Google Scholar 

  • Levi G, Gumbiner B, Thiery JP (1991) The distribution of E-cadherin during Xenopus laevis development. Development 111:159–169

    Article  CAS  PubMed  Google Scholar 

  • Lillywhite HB, Maderson PFA (1982) Skin structure and permeability. In: Gans CC, Pough FH (eds) Biology of the reptilia, vol 12. Academic Press, New York, pp 397–442

    Google Scholar 

  • Maderson PFA (1965) The embryonic development of the squamate integument. Acta Zool 46:275–298

    Article  Google Scholar 

  • Maderson PFA (1985) Some developmental problems of the reptilian integument. In: Gans C, Billett F, Maderson PFA (eds) Biology of Reptilia: Development. Johm Wiley & Sons, New York, pp 525–598

    Google Scholar 

  • Maderson PFA, Rabinowitz T, Tandler B, Alibardi L (1998) Ultrastructural contributions to an understanding of the cellular mechanisms involved in lizard skin shedding with comments on the function and evolution of a unique lepidosaurian phenomenon. J Morphol 236:1–24

    Article  CAS  PubMed  Google Scholar 

  • Menon GK, Maderson PFA, Drewes RC, Baptista LF, Price LF, Elias PM (1996) Ultrastructural organization of avian stratum corneum lipids as the basis for facultative cutaneous waterproofing. J Morphol 227:1–13

    Article  CAS  PubMed  Google Scholar 

  • Muller-Rover S, Tokura Y, Welker P, Furukawa F, Wakita H, Takigawa M, Paus R (1999) E- and P-cadherin expression during murine hair follicle morphogenesis and cycling. Exp Dermatol 8:237–246

    Article  CAS  PubMed  Google Scholar 

  • Musser JM, Wagner GP, Prum RO (2015) Nuclear β-catenin localization supports homology of feathers, avian scutate scales, and alligator scales in early development. Evol Dev 17:185–194

    Article  CAS  PubMed  Google Scholar 

  • Roth SI, Jones WA (1970) The ultrastructure of epidermal maturation in the skin of the boa constrictor (Constrictor constrictor). J Ultrastr Res 32:69–93

    Article  CAS  Google Scholar 

  • Sawyer RH, Knapp LW (1986) O’Guin WM (1986) The skin of birds: epidermis, dermis, and appendages. In: Bereither-Hahn J, Matoltsy AG, Richards KS (eds) Biology of the integument, vol II. Springer, Berlin, pp 194–238

    Chapter  Google Scholar 

  • Serras F, Fraser S, Chuong CM (1993) Asymmetric patterns of gap junctional communication in developing chicken skin. Development 119:85–96

    Article  CAS  PubMed  Google Scholar 

  • Shames RB, Jennings AG, Sawyer RH (1991) Expression of the cell adhesion molecules, L-CAM and N-CAM during avian scale development. J Exp Zool 257:195–207

    Article  CAS  PubMed  Google Scholar 

  • Shine R (1998) Australian snakes. Reed New Holland Publisher, Sydney

    Google Scholar 

  • Swadzba E, Maslak R, Rupik W (2009) Light and scanning microscopic studies of integument differentiation in the grass snake Natrix natrix L. (Lepidosauria, Serpentes) during embryogenesis. Acta Zool 90:30–41

    Article  Google Scholar 

  • Swadzba E, Rupik W (2010) Ultrastructural studies of epidermis keratinization in grass snake embryos Natrix natrix L. (Lepidosauria, Serpentes) during late embryogenesis. Zoology 13:339–360

    Article  Google Scholar 

  • Tu MC, Lillywhite HB, Menon JG, Menon GK (2002) Postnatal ecdysis establishes the permeability barrier in snake skin: New insights into lipid barrier structures. J Exp Biol 205:3019–3030

    Article  CAS  PubMed  Google Scholar 

  • Tunggal JA, Helfrich I, Schmitz A, Scharz H, Gunzel D, Fromm M, Kemler R, Krieg T, Niessen CN (2005) E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 24:1146–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Widelitz RB, Jiang TX, Nooven A, Ting-Berreth SA, Yin E, Jung HS, Chuong MC (1997) Molecular histology in skin appendage morphogenesis. Micr Res Techn 38:452–465

    Article  CAS  Google Scholar 

  • Wu P, Alibardi L, Chuong CM (2014) Lizard scale regeneration and development: a model system to analyze mechanisms of skin appendages morphogenesis in amniotes. Regeneration 1:16–26

    CAS  Google Scholar 

  • Zayed AE, Ahmed YA, El-Hafez EA, Steger K (2012) Connexin 43 expression and its possible role in skin development. J Med Sci 12:168–174

    Article  Google Scholar 

  • Zehr DR (1962) Stages in the normal development of the common garter snake, Thamnophis sirtalis sirtalis. Copeia 2:322–329

    Article  Google Scholar 

  • Zhang XF, Cui X (2017) Connexin 43: key role in the skin (Review). Biomed Reports 6:605–611

    Article  CAS  Google Scholar 

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  1. Comparative Histolab, Padua, Italy

    Lorenzo Alibardi

  2. Dipartimento Di Biologia, Universita Di Bologna, via Selmi 3, 40126, Bologna, Italy

    Lorenzo Alibardi

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Alibardi, L. Cell adhesion and junctional proteins in the developing skin of snakes indicate they coordinate the differentiation of the epidermis. Protoplasma 259, 981–998 (2022). https://doi.org/10.1007/s00709-021-01711-4

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