Acta Biotheoretica

, Volume 63, Issue 3, pp 283–294 | Cite as

A Conceptual Model of Morphogenesis and Regeneration

  • A. Tosenberger
  • N. Bessonov
  • M. Levin
  • N. Reinberg
  • V. Volpert
  • N. Morozova
Regular Article

Abstract

This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species (e.g. planaria and salamanders) are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells—e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration.

Keywords

Regeneration Morphogenesis Cell memory Target morphology 

Notes

Acknowledgments

The authors acknowledge the National Institute of Health, NIH R03 HD81401-01, 1R01HD081326-01; The G. Harold and Leila Y. Mathers Charitable Foundation; NSF CDI EF-1124651; W.M. Keck foundation; Agence National de la Recherch, ANR-2010-BLAN-0107-01.

Supplementary material

10441_2015_9249_MOESM1_ESM.pdf (601 kb)
Supplementary material 1 (pdf 601 KB)

References

  1. Baddour JA, Sousounis K, Tsonis PA (2012) Organ repair and regeneration: an overview. Birth Defects Res C Embryo Today 96:1–29CrossRefGoogle Scholar
  2. Bessonov N, Levin M, Morozova N, Reinberg N, Tosenberger A, Volpert V (2015) On a model of pattern regeneration based on cell memory. PLoS One 10(2):e0118091. doi: 10.1371/journal.pone.0118091
  3. Birnbaum KD, Alvarado AS (2008) Slicing across kingdoms: regeneration in plants and animals. Cell 132:697–710CrossRefGoogle Scholar
  4. Bouwmeester T (2001) The Spemann-Mangold organizer: the control of fate specification and morphogenetic rearrangements during gastrulation in Xenopus. Int J Dev Biol 45:251–258Google Scholar
  5. Doursat R, Sayama H, Michel O (2013) A review of morphogenetic engineering. Nat Comput 12:517–535CrossRefGoogle Scholar
  6. Farinella-Ferruzza N (1956) The transformation of a tail into a limb after xenoplastic transformation. Experientia 15:304–305CrossRefGoogle Scholar
  7. French V (1980) Positional information around the segments of the cockroach leg. J Embryol Exp Morphol 59:281–313Google Scholar
  8. Illingworth CM (1974) Trapped fingers and amputated finger tips in children. J Pediatr Surg 9:853–858CrossRefGoogle Scholar
  9. Kamm RD, Bashir R (2014) Creating living cellular machines. Ann Biomed Eng 42:445–459CrossRefGoogle Scholar
  10. Kish PE, Bohnsack BL, Gallina D, Kasprick DS, Kahana A (2011) The eye as an organizer of craniofacial development. Genesis 49:222–230CrossRefGoogle Scholar
  11. Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460:60–65CrossRefGoogle Scholar
  12. Levin M (2011) The wisdom of the body: future techniques and approaches to morphogenetic fields in regenerative medicine, developmental biology and cancer. Regen Med 6:667–673CrossRefGoogle Scholar
  13. Levin M (2012) Morphogenetic fields in embryogenesis, regeneration, and cancer: non-local control of complex patterning. Biosystems 109:243–261CrossRefGoogle Scholar
  14. Levin M, Stevenson C (2012) Regulation of cell behavior and tissue patterning by bioelectrical signals: challenges and opportunities for biomedical engineering. Annu Rev Biomed Eng 14:295–323CrossRefGoogle Scholar
  15. Levin M (2014) Endogenous bioelectrical networks store non-genetic patterning information during development and regeneration. J Physiol 592:2295–2305CrossRefGoogle Scholar
  16. Li C (2012) Deer antler regeneration: a stem cell-based epimorphic process. Birth Defects Res C Embryo Today 96:51–62CrossRefGoogle Scholar
  17. Mao Sa, Glorioso JM, Nyberg SL (2014) Liver regeneration. Transl Res 163:352–362CrossRefGoogle Scholar
  18. Morozova N, Shubin M (2012) The geometry of morphogenesis and the morphogenetic field concept. Pattern formation in morphogenesis—problems and mathematical issues. Springer Proceedings in Mathematics 15:255–282Google Scholar
  19. Morozova N, Penner R (2015) Geometry of Morphogenesis, BIOMAT 2014, World Scientific Proceedings of the International Symposium on Mathematical and Computational Biology. Mondaini R (ed), in pressGoogle Scholar
  20. Mustard J, Levin M (2014) Bioelectrical mechanisms for programming growth and form: taming physiological networks for soft body robotics. Soft Robot 1:169–191CrossRefGoogle Scholar
  21. Rubin H (1985) Cancer as a dynamic developmental disorder. Cancer Res 45:2935–2942Google Scholar
  22. Sousounis K, Baddour JA, Tsonis PA (2014) Aging and regeneration in vertebrates. Curr Top Dev Biol 108:217–246CrossRefGoogle Scholar
  23. Vandenberg LN, Levin M (2010) Consistent left-right asymmetry cannot be established by late organizers in Xenopus unless the late organizer is a conjoined twin. Development 137:1095–1105CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • A. Tosenberger
    • 1
  • N. Bessonov
    • 2
  • M. Levin
    • 3
  • N. Reinberg
    • 2
  • V. Volpert
    • 4
  • N. Morozova
    • 1
    • 5
  1. 1.Institut des Hautes Études ScientifiquesBures-sur-YvetteFrance
  2. 2.Institute of Mechanical Engineering ProblemsSaint PetersburgRussia
  3. 3.Department of Biology, Tufts Center for Regenerative & Developmental BiologyTufts UniversityMedfordUSA
  4. 4.Institut Camille Jordan, UMR 5208 CNRSUniversity Lyon 1VilleurbanneFrance
  5. 5.Laboratoire Epigenetique et Cancer, CNRS FRE 3377CEA SaclayGif-sur-YvetteFrance

Personalised recommendations