Skip to main content
Log in

On some structural and evolutionary aspects of rDNA amplification in oogenesis of Trachemys scripta turtles

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The features of rDNA amplification have been studied in oocytes of the red-eared slider Trachemys scripta using a number of specific histochemical and cytomolecular methods. A single nucleolus in early diplotene oocytes is associated with the nucleolus organizer region (NOR). With oocyte growth, the number of nucleoli increases dramatically and reaches hundreds by the lampbrush chromosome stage (pre-vitellogenesis). RNA-polymerase I, fibrillarin, and PCNA immunodetection in the amplified nucleoli and FISH of the 5’ETS probe to the oocyte nuclear content suggest pre-rRNA and rDNA synthesis in the nucleoli at all stages studied. This implies a continuous reproduction of the nucleoli during oocyte development from early diplotene up to vitellogenesis. The data obtained offer a different way for rDNA amplification and formation of extrachromosomal nucleoli in turtle oocytes compared with the amplified nucleoli formation in amphibian and fish oocytes. In the Sauropsida clade of Archelosauria, which includes turtles, crocodiles, and birds, rDNA function is known to be suppressed in avian oogenesis during the lampbrush stage (Gaginskaya et al. in Cytogenet Genome Res 124:251–267, 2009).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Andrade LEC, Chan EKL, Raska I, Peebles CL, Roos G, Tan EM (1991) Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J Exp Med 173:1407–1419

    CAS  PubMed  Google Scholar 

  • Arronet VN (1973) Morphological changes of nucleolar structure in the oogenesis of reptiles (Lacertidae, Agamidae). J Herpetol 7:163–193

    Google Scholar 

  • Bachvarova R (1985) Gene expression during oogenesis and oocyte development in mammals. In: Browder L.W. (eds) Oogenesis. Developmental Biology (A Comprehensive Synthesis), vol 1. Springer, Boston, MA

  • Bakken AH (1975) Replication of amplifying ribosomal deoxyribonucleic acid in rolling circles in Xenopus laevis oocytes. J Histochem Cytochem 23(7):463–474

    CAS  PubMed  Google Scholar 

  • Bartholomé O, Franck C, Piscicelli P, Lalun N, Defourny J, Renauld J, Thelen N, Lamaye F, Ploton D, Thiry M (2019) Relationships between the structural and functional organization of the turtle cell nucleolus. J Struct Biol 208(3):107398. https://doi.org/10.1016/j.jsb.2019.09.015

    Article  CAS  PubMed  Google Scholar 

  • Bellairs R (1965) The relationship between oocyte and follicle in the hen’s ovary as shown by electron microscopy. J Embryol Exp Morphol 13:215–233

    CAS  PubMed  Google Scholar 

  • Betz TW (1963) The ovarian histology of the diamond-backed water snake, Natrix rhombifera during the reproductive cycle. J Morphol 113:245–260

    CAS  PubMed  Google Scholar 

  • Beyo RS, Sreejith P, Divya L, Oommen OV, Akbarsha MA (2007) Ultrastructural observations of previtellogenic ovarian follicles of the caecilians Ichthyophis tricolor and Gegeneophis ramaswamii. J Morphol 268:329–342

    PubMed  Google Scholar 

  • Brangwynne CP, Mitchison TJ, Hyman AA (2011) Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci U S A 108(11):4334–4339

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brown DD, Dawid I (1968) Specific gene amplification in oocytes. Science 160:272–280

    CAS  PubMed  Google Scholar 

  • Callan HG (1986) Lampbrush chromosomes. Springer, Heidelberg

    Google Scholar 

  • Callebaut M, Van Nassauw L, Harrisson F (1997) Comparison between oogenesis and related ovarian structures in a reptile, Pseudemys scripta elegans (turtle) and in a bird Coturnix coturnix japonica (quail). Reprod Nutr Dev 37(3):233–252

    CAS  PubMed  Google Scholar 

  • Chan P, Frakes R, Tan EM, Brattain MG, Smetana K, Busch H (1983) Indirect immunofluorescence studies of proliferating cell nuclear antigen in nucleoli of human tumor and normal tissues. Cancer Res 43(8):3770–3777

    CAS  PubMed  Google Scholar 

  • Chiari Y, Cahais V, Galtier N, Delsuc F (2012) Phylogenomic analyses support the position of turtles as the sister group of birds and crocodiles (Archosauria). BMC Biol. https://doi.org/10.1186/1741-7007-10-65

  • Cleiton F, Giuliano-Caetano L (2008) Cytogenetic characterization of two turtle species: Trachemys dorbigni and Trachemys scripta elegans. Caryologia. https://doi.org/10.1080/00087114.2008.10589637

  • Coggins LW, Gall JG (1972) The timing of meiosis and DNA synthesis during early oogenesis in the toad, Xenopus laevis. J cell biol doi. https://doi.org/10.1083/jcb.52.3.569

  • Correll CC, Bartek J, Dundr M (2019) The nucleolus: a multiphase condensate balancing ribosome synthesis and translational capacity in health, aging and ribosomopathies. Cells. https://doi.org/10.3390/cells8080869

  • Crawford NG, Faircloth BC, McCormack JE, Brumfield RT, Winker K, Glenn TC (2012) More than 1000 ultraconserved elements provide evidence that turtles are the sister group of archosaurs. Biol Lett. https://doi.org/10.1098/rsbl.2012.0331

  • Crawford NG, Parham JF, Sellas AB, Faircloth BC, Glenn TC, Papenfuss TJ, Henderson JB, Hansen MH, Simison WB (2015) A phylogenomic analysis of turtles. Mol Phylogenet Evol 83:250–257

    PubMed  Google Scholar 

  • Davidian AG, Koshel EI, Lavrova OB, Dyomin AG, Galkina SA, Saifitdinova AF, Gaginskaya ER (2017) Functional features of the nucleolar organizer in developing oocytes of juvenile birds. Russ J Dev Biol 48:224–230

    CAS  Google Scholar 

  • Davidson EH (1986) Gene activity in early development, 3rd edn. Academic Press, New York

    Google Scholar 

  • Diaz-Andrade MC, Galíndez EJ, López-Cazorla A, Estecondo S (2011) Ovarian folliculogenesis in the smallnose fanskate Sympterygia bonapartii (Müller & Henle, 1841) (Chondrichthyes, Rajidae). Int J Morphol 29(1):174–181

    Google Scholar 

  • Dondua AK (2018) Developmental biology. SPbU Press, Saint-Petersburg

    Google Scholar 

  • Dubois ML, Boisvert FM (2016) The nucleolus: structure and function. In: Bazett-Jones D, Dellaire G (eds) The functional nucleus. Springer, Cham. https://doi.org/10.1007/978-3-319-38882-3_2

    Chapter  Google Scholar 

  • Feric M, Vaidya N, Harmon TS, Mitrea DM, Zhu L, Richardson TM, Kriwacki RW, Pappu RV, Brangwynne CP (2016) Coexisting liquid phases underlie nucleolar subcompartments. Cell 165(7):1686–1697

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ficq A, Brachet J (1971) RNA-dependent DNA polymerase: possible role in the amplification of ribosomal DNA in Xenopus oocytes. Proc Natl Acad Sci U S A 68(11):2774–2776

    CAS  PubMed  PubMed Central  Google Scholar 

  • Flynx TT, Hill JP (1939) The development of the Monotremata. Part IV. Growth of the ovarian ovum, maturation, fertilization and early cleavage. Transactions of the Zoological Society of London. https://doi.org/10.1111/j.1096-3642.1939.tb00588.x

  • Gaginskaya ER (1972) Nuclear structures in oocytes of adult birds. II Protein bodies and the karyosphere. Tsitologiia 14(5):568–578

    CAS  Google Scholar 

  • Gaginskaya ER, Gruzova MN (1969) Peculiarities of the oogenesis in chaffinch. Tsitologiia 11:1241–1251

    CAS  Google Scholar 

  • Gaginskaya E, Kulikova T, Krasikova A (2009) Avian lampbrush chromosomes: a powerful tool for exploration of genome expression. Cytogenet Genome Res 124:251–267

    CAS  PubMed  Google Scholar 

  • Gall JG (1968) Differential synthesis of the genes for rRNA during amphibian oogenesis. Proc Natl Acad Sci U S A 60:553–560

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gall JG, Pardue ML (1969) Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A 63(2):378–383

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grier HJ, Uribe MC, Nostro FLL, Mims SD, Parenti LR (2016) Conserved form and function of the germinal epithelium through 500 million years of vertebrate evolution. J Morphol 277:1014–1044

    PubMed  Google Scholar 

  • Griffiths M (1978) The biology of Monotremes. Academic Press, New York

    Google Scholar 

  • Grummt I (2010) Wisely chosen paths—regulation of rRNA synthesis. FEBS J 277:4626–4639

    CAS  PubMed  Google Scholar 

  • Grummt I (2013) The nucleolus—guardian of cellular homeostasis and genome integrity. Chromosoma 122:487–497

    CAS  PubMed  Google Scholar 

  • Guide for the Care and Use of Laboratory Animals, 8th edition (2011). Washington, DC: The National Academies Press. https://doi.org/10.17226/12910

  • Guillette LJ Jr, Cree A (1997) Morphological changes in the corpus luteum of tuatara (Sphenodon punctatus) during gravidity. J Morphol 232(1):79–91

    PubMed  Google Scholar 

  • Guraya SS (1989) Ovarian follicles in reptiles and birds. Springer-Verlag, Berlin

    Google Scholar 

  • Hernandez-Verdun D, Roussel P, Thiry M, Sirri V, Lafontaine DLJ (2010) The nucleolus: structure/function relationship in RNA metabolism. Wiley Interdiscip Rev RNA 1:415–431

    CAS  PubMed  Google Scholar 

  • Hubert J, Andrivon C (1971) Preliminary data on the incorporation of radio-active precursors by ovocytes and ovary follicles of young viviparous lizards (Lacerta vivipara Jacquin). C R Acad Hebd Seances Acad Sci D 273(17):1521–1523

    CAS  PubMed  Google Scholar 

  • Kass S, Tyc K, Steitz J, Sollner-Webb B (1990) The U3 small nucleolar ribonucleoprotein functions in the first step of preribosomal RNA processing. Cell 60:897–908

    CAS  PubMed  Google Scholar 

  • Klosterman LL (1983) The ultrastructure of germinal beds in the ovary of Gerrhonotus coeruleus (Reptilia: Anguidae). J Morphol 178:247–265

    CAS  PubMed  Google Scholar 

  • Koshel EI, Galkina SA, Saifitdinova AF, Dyomin AG, Deryusheva SE, Gaginskaya ER (2016) Ribosomal RNA gene functioning in avian oogenesis. Cell Tissue Res 366:533–542

    CAS  PubMed  Google Scholar 

  • Kress A, Merry NE, Selwood L (2001) Oogenesis in the marsupial stripe-faced dunnart, Sminthopsis macroura. Cells Tissues Organs 168(3):188–202

    CAS  PubMed  Google Scholar 

  • Lamaye F, Galliot S, Alibardi L, Lafontaine DLJ, Thiry M (2011) Nucleolar structure across evolution: the transition between bi- and tricompartmentalized nucleoli lies within the class Reptilia. J Struct Biol 174(2):352–359

    CAS  PubMed  Google Scholar 

  • Le Menn F, Benneteau-Pelissero C, Le Menn R (2018) An updated version of histological and ultrastructural studies of oogenesis in the Siberian sturgeon Acipenser baerii. In: Williot P, Nonnotte G, Vizziano-Cantonnet D, Chebanov M (eds) The Siberian sturgeon (Acipenser baerii, Brandt, 1869), vol 1. Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-61664-3_14

    Chapter  Google Scholar 

  • Lewis JC, McMillan DB (1965) The development of the ovary of the sea lamprey (Petromyzon marinus L.). J Morphol 117:425–466

    CAS  PubMed  Google Scholar 

  • Liu J, Organ C, Benton M, Brandley M, Aitchison J (2017) Live birth in an archosauromorph reptile. Nat Commun. https://doi.org/10.1038/ncomms14445

  • Lozano A, Ramírez-Bautista A, Uribe MC (2014) Oogenesis and ovarian histology in two populations of the viviparous lizard Sceloporus grammicus (Squamata: Phrynosomatidae) from the central Mexican Plateau. J Morphol 275:949–960

    PubMed  Google Scholar 

  • Macgregor HC (1968) Nucleolar DNA in oocytes of Xenopus laevis. J Cell Sci 3:417–444

    Google Scholar 

  • Macgregor HC (1972) The nucleolus and its genes in amphibian oogenesis. Biol Rev Camb Philos Soc 47:177–210

    CAS  PubMed  Google Scholar 

  • Macgregor HC (1982) Ways of amplifying ribosomal genes. In: Jordan EG, Cullis CA (eds) The nucleolus. Cambridge University Press, Cambridge, pp 129–151

    Google Scholar 

  • Macgregor H, Klosterman L (1979) Observations on the cytology of Bipes (Amphisbaenia) with special reference to its lampbrush chromosomes. Chromosoma 72:67–87

    Google Scholar 

  • Mais C, Scheer U (2001) Molecular architecture of the amplified nucleoli of Xenopus oocytes. J Cell Sci 114:709–718

    CAS  PubMed  Google Scholar 

  • Mais C, McStay B, Scheer U (2002) On the formation of amplified nucleoli during early Xenopus oogenesis. J Struct Biol 140(1–3):214–226

    CAS  PubMed  Google Scholar 

  • Meyer A, Zardoya R (2003) Recent advances in the (molecular) phylogeny of vertebrates. Annu Rev Ecol Evol Syst 34(1):311–338

    Google Scholar 

  • Miller OL, Beatty BR (1969) Extrachromosomal nucleolar genes in amphibian oocytes. Genetics 61(1):133–143

    Google Scholar 

  • Moore BC, Uribe-Aranzábal MC, Boggs AS, Guillette LJ (2008) Developmental morphology of the neonatal alligator (Alligator mississippiensis) ovary. J Morphol 269:302–312

    PubMed  Google Scholar 

  • Motta CM, Andreuccetti P, Filosa S (1991) Ribosomal gene amplification in oocytes of the lizard Podarcis sicula. Mol Reprod Dev 29:95–102

    CAS  PubMed  Google Scholar 

  • Nainan H, Ping Y, Yang Y, Jinxiong L, Huijun B, Haili L, Hui Z, Qiusheng C (2010) Fine structural observation on the oogenesis and vitellogenesis of the Chinese soft-shelled turtle (Pelodiseus sinensis). Zygote 18(2):109–120

    Google Scholar 

  • Nizami ZF, Gall JG (2012) Pearls are novel Cajal body-like structures in the Xenopus germinal vesicle that are dependent on RNA pol III transcription. Chromosom Res 20:953–969

    CAS  Google Scholar 

  • Nizami Z, Deryusheva S, Gall JG (2010) The Cajal body and histone locus body. Cold Spring Harb Perspect Biol 2:a000653. https://doi.org/10.1101/cshperspect.a000653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ochs RL, Stein TW, Tan EM (1994) Coiled bodies in the nucleolus of breast cancer cells. J Cell Sci 107:385–399

    CAS  PubMed  Google Scholar 

  • Ogawa LM, Baserga SJ (2017) Crosstalk between the nucleolus and the DNA damage response. Mol BioSyst 13(3):443–455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pederson T (2011) The nucleolus. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a000638

  • Penzo M, Montanaro L, Treré D, Derenzini M (2019) The ribosome biogenesis—Cancer connection. Cells. https://doi.org/10.3390/cells8010055

  • Pérez-Bermúdez E, Ruiz-Urquiola A, Lee-González I, Petric B, Almaguer-Cuenca N, Sanz-Ochotorena A, Espinosa–López G (2012) Ovarian follicular development in the hawksbill turtle (Cheloniidae: Eretmochelys imbricata L.). J Morphol 273:1338–1352

    PubMed  Google Scholar 

  • Perkowska E, Macgregor HC, Birnstiel ML (1968) Gene amplification in the oocyte nucleus of mutant and wild-type Xenopus laevis. Nature 217:649–650

    CAS  PubMed  Google Scholar 

  • Press N (1964) An unusual organelle in avian ovaries. J Ultrastruct Res 10:528–546

    CAS  PubMed  Google Scholar 

  • Prisco M, Ricchiari L, Montella R, Liguoro A, Andreuccetti P (2004) The nucleolus and its modifications during oogenesis of Torpedo marmorata. J Fish Biol 65:1489–1497

    Google Scholar 

  • Rahil KS, Narbaitz R (1973) Ultrastructural studies on the relationship between follicular cells and growing oocytes in the turtle Pseudemys scripta elegans. J Anat 115(2):175–186

    CAS  PubMed  PubMed Central  Google Scholar 

  • Raikova EV (1976) Evolution of the nucleolar apparatus during oogenesis in Acipenseridae. J Embryol Exp Morphol 35:667–687

    CAS  PubMed  Google Scholar 

  • Ricchiari L, Prisco M, Tammaro MCM, Pugliese I, Andreucetti P (2003) Spherical bodies present within the germinal vesicle of Podacris sicula previtellogenic oocyte derive from the temporaneous inactivation of ribosomal genes. Mol Reprod Dev 64(3):321–328

    CAS  Google Scholar 

  • Rückert J (1892) Zur entwickelungsgeschichte des ovarialeies bei selachiern. Anat Anz 7:107–158

    Google Scholar 

  • Saifitdinova A, Galkina S, Volodkina V, Gaginskaya E (2017) Preparation of lampbrush chromosomes dissected from avian and reptilian growing oocytes. Bio Comm 62(3):165–168

    Google Scholar 

  • Schjeide OA, Galey F, Grellert EA, I-San Lin R, De Vellis J, Mead JF (1970) Macromolecules in oocyte maturation. Biol Reprod 2(2):14–43

    Google Scholar 

  • Schjeide OA, Kancheva L, Hanzely L, Briles WE (1975) Production and fates of unique organelles (transosomes) in ovarian follicles of Gallus domesticus under various conditions. II. Cell Tissue Res 163:63–79

    CAS  PubMed  Google Scholar 

  • Selwood L, Johnson M (2006) Trophoblast and hypoblast in the monotreme, marsupial and eutherian mammal: evolution and origins. Bioessays 28:128–145

    PubMed  Google Scholar 

  • Spring H, Meissner B, Fischer R, Mouzaki D, Trendelenburg M (1996) Spatial arrangement of intra-nucleolar rDNA chromatin in amplified Xenopus oocyte nucleoli: structural changes precede the onset of rDNA transcription. Int J Dev Biol 40:263–272

    CAS  PubMed  Google Scholar 

  • Taddei C (1972) Ribosome arrangement during oogenesis of Lacerta sicula Raf. Exper Cell Res 70(2):285–292

    CAS  Google Scholar 

  • Thiry M, Lafontaine DLJ (2005) Birth of a nucleolus: the evolution of nucleolar compartments. Trends Cell Biol 15(4):194–199

    CAS  PubMed  Google Scholar 

  • Thiry M, Poncin P (2005) Morphological changes of the nucleolus during oogenesis in oviparous teleost fish, Barbus barbus (L.). J Struct Biol 152(1):1–13

    CAS  PubMed  Google Scholar 

  • Thiry M, Lamaye F, Lafontaine DLJ (2011) The nucleolus: when 2 became 3. Nucleus 2(4):289–293

    PubMed  Google Scholar 

  • Tian Q, Kopf GS, Brown RS, Tseng H (2001) Function of basonuclin in increasing transcription of the ribosomal RNA genes during mouse oogenesis. Development 128:407–416

    CAS  PubMed  Google Scholar 

  • Trivett MK, Potter IC, Power G, Zhou H, Macmillan DL, Martin TJ, Danks JA (2005) Parathyroid hormone-related protein production in the lamprey Geotria australis: developmental and evolutionary perspectives. Dev Genes Evol 215:553–563

    CAS  PubMed  Google Scholar 

  • Turowski TW, Tollervey D (2015) Cotranscriptional events in eukaryotic ribosome synthesis. RNA 6:129–139

    CAS  PubMed  Google Scholar 

  • Ullmann SL, Butcher L (1996) Mammalian oocyte organelles with special reference to pleomorphic mitochondria and vacuole formation in marsupials. Reprod Fertil Dev 8(4):491–508

    CAS  PubMed  Google Scholar 

  • Uribe MCA, Guillette LJ (2000) Oogenesis and ovarian histology of the American alligator Alligator mississippiensis. J Morphol 245:225–240

    CAS  PubMed  Google Scholar 

  • Verheggen C, Le Panse S, Almouzni G, Hernandez-Verdun D (1998) Presence of pre-rRNAs before activation of polymerase I transcription in the building process of nucleoli during early development of Xenopus laevis. J Cell Biol 142(5):1167–1180

    CAS  PubMed  PubMed Central  Google Scholar 

  • Verheggen C, Almouzni G, Hernandez-Verdun D (2000) The ribosomal RNA processing machinery is recruited to the nucleolar domain before RNA polymerase I during Xenopus laevis development. J Cell Biol 149(2):293–306

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vieira S, de Pérez GR, Ramírez-Pinilla MP (2010) Ultrastructure of the ovarian follicles in the placentotrophic Andean lizard of the genus Mabuya (Squamata: Scincidae). J Morphol 271:738–749

    PubMed  Google Scholar 

  • Vincent WS, Halvorson HO, Chen H-R, Shin D (1969) A comparison of ribosomal gene amplification in uni- and multinucleolate oocytes. Exp Cell Res 57(2):240–250

    CAS  PubMed  Google Scholar 

  • Yang XC, Burch BD, Yan Y, Marzluff WF, Dominski Z (2009) FLASH, a proapoptotic protein involved in activation of caspase-8, is essential for 3′ end processing of histone pre-mRNAs. Mol Cell 36(2):267–278

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zagris N, Kalantzis K, Guialis A (1998) Activation of embryonic genome in chick. Zygote 6:227–231

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are sincerely grateful to J. Gall for kindly providing R288 serum against p80, to S. Deryusheva for anti-FLASH antibodies, D. Bogolyubov and G. Pochukalina for the anti-RNA-polymerase I and dsDNA antibodies, S. Naryzhny and E. Novikova for anti-PCNA antibodies, I. Aparin for U3 snoRNA probe, and to Alisa Guseva for the linguistic review and proofreading of the manuscript. The analytical facilities were provided by “Chromas” Resource Center of the Saint Petersburg State University Scientific Park.

Funding

This study was sponsored by Russian Foundation for Basic Research (project #18-04-01276A) and Saint Petersburg State University’s Initiative 4 (project #1.40.1625.2017).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elena Gaginskaya.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the Ethical Committee of St. Petersburg State University (Statement #131-03-3 issued 01.06.2017) and Guide for the Care and Use of Laboratory Animals (2011).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Davidian, A., Koshel, E., Dyomin, A. et al. On some structural and evolutionary aspects of rDNA amplification in oogenesis of Trachemys scripta turtles. Cell Tissue Res 383, 853–864 (2021). https://doi.org/10.1007/s00441-020-03282-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03282-x

Keywords

Navigation