ORIGIN OF ENTERIC NERVOUS SYSTEM CELLS AND MIGRATION PATHWAYS DURING EMBRYONIC DEVELOPMENT

  • Milos Djuknic University of Belgrade, Faculty of Medicine, Belgrade, Republic of Serbia
  • Nela Puskas University of Belgrade, Faculty of Medicine, Institute of Histology and Embryology „Prof. dr Aleksandar Đ. Kostić“, Belgrade, Republic of Serbia
  • Milica Labudovic Borovic University of Belgrade, Faculty of Medicine, Institute of Histology and Embryology „Prof. dr Aleksandar Đ. Kostić“, Belgrade, Republic of Serbia
  • Radmila Jankovic University of Belgrade, Faculty of Medicine, Institute of Pathology „Prof. dr Đordje Joannović“, Belgrade, Republic of Serbia
Keywords: enteric nervous system, embryonic development, cell migration, Hirschsprung disease

Abstract


The enteric nervous system (ENS) is represented by a complex network of neurons, glial and other cells within the wall of the digestive tract. ENS is responsible for numerous, vital functions in our body. Thus, ENS regulates motility of the digestive tract, secretion into the intestinal lumen, exchange of fluid and electrolytes through the mucosa, as well as mucosal perfusion. In order to perform these important functions, proper embryonic development of ENS is necessary. ENS cells are derived from precursor cells of the neural crest (NCCs – neural crest cells). Two cell populations that contribute to the largest number of future ENS cells are the vagal and sacral NCCs. Vagal NCCs enter the primitive gut tube in the region of the future esophagus (foregut), and begin their migration, through the midgut towards the hindgut and the future anal region. Sacral NCCs enter the hindgut region following the extrinsic nerve fibers and continue their migration rostrally, towards vagal NCCs. Along with the migration process, these cells undergo other important processes, such as proliferation, neuro-glial differentiation, gangliogenesis, axonal pathway formation and synaptogenesis. All these processes are strictly regulated by numerous signaling pathways, which are still being actively researched. Modern lineage tracing and other technologies, that enabledfollowing of individual precursor cells through their development pathways, will significantly contribute to the better understanding of development of ENS. This may have repercussions in improving the diagnosis and treatment of some developmental (Hirschsprung disease) and other ENS disorders.

References

1. Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol
2012; 9(5): 286-94. doi: 10.1038/nrgastro.2012.32

2. Hansen MB. The enteric nervous system I: organization and classification. Pharmacol Toxicol 2003; 92(3):105-13. doi:10.1034/j.1600-0773.2003.t01-1-920301.x

3. Lestarevic S, Lazic M, Jankovic R. Distribution and quantification of elements of the enteric nervous system in the distal rectum of neonates and infants: PS038. Porto Biomed J 2017; 2(5):200. doi:10.1016/j.pbj.2017.07.059

4. Fung C, Vanden Berghe P. Functional circuits and signal processing in the enteric nervous system. Cell Mol Life Sci2020; 77: 4505-22. doi:10.1007/s00018-020-03543-6

5. Furness JB, Callaghan BP, Rivera LR, Cho HJ. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol 2014; 817: 39-71. doi:10.1007/978-1-4939-0897-4_3

6. Schneider S, Wright CM, Heuckeroth RO. Unexpected roles for the second brain: enteric nervous system as master regulator of bowel function. Annu Rev Physiol 2019; 81: 235-59. doi:10.1146/annurev-physiol-021317-121515

7. Jankovic R. Modern diagnostics of Hirschsprung disease and related disorders. Materia medica 2016; 32(2):1478-82.

8. Jankovic R. Analysis of glial cell index and interstitial cells of Cajal in colorectal biopsies of children with Hirschsprung disease and related disorders [doctoral dissertation]. Belgrade: Faculty of Medicine, University of Belgrade; 2016.

9. Pawolski W, Schmidt MHH. Neuron-Glia Interaction in the Developing and Adult Enteric Nervous System. Cells 2021; 10(1):47. doi:10.3390/cells10010047

10. Rao M, Gershon MD. Enteric nervous system development: what could possibly go wrong? Nat Rev Neurosci 2018; 19(9):552-65. doi: 10.1038/s41583-018-0041-0

11. Nagy N, Goldstein AM. Enteric nervous system development: A crest cell’s journey from neural tube
to colon. Semin Cell Dev Biol 2017; 66:94-106. doi:10.1016/j.semcdb.2017.01.006

12. Obermayr F, Hotta R, Enomoto H, Young HM. Development and developmental disorders of the enteric nervous system. Nat Rev Gastroenterol Hepatol 2013;10(1):43-57. doi: 10.1038/nrgastro.2012.234

13. Diposarosa R, Bustam NA, Sahiratmadja E, Susanto PS, Sribudiani Y. Literature review: enteric nervous system development, genetic and epigenetic regulation in the etiology of Hirschsprung’s disease. Heliyon 2021;7(6):e07308. doi: 10.1016/j.heliyon.2021.e07308

14. Yntema CL, Hammond WS. The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J Comp Neurol 1954; 101(2):515-41. doi:10.1002/cne.901010212

15. Le Douarin NM. Cell line segregation during peripheral nervous system ontogeny. Science 1986; 231(4745): 1515-22. doi: 10.1126/science.3952494

16. Bronner ME, Le Douarin NM. Development and evolution of the neural crest: an overview. Dev Biol 2012; 366(1):2-9. doi: 10.1016/j.ydbio.2011.12.042

17. Kuo BR, Erickson CA. Regional differences in neural crest morphogenesis. Cell Adh Migr 2010; 4(4):567-85. doi:10.4161/cam.4.4.12890

18. Young HM, Bergner AJ, Simpson MJ, McKeown SJ, Hao MM, Anderson CR et al. Colonizing while migrating: how do individual enteric neural crest cells behave? BMC Biol 2014; 12:23. doi:10.1186/1741-7007-12-23

19. Goldstein AM, Hofstra RM, Burns AJ. Building a brain in the gut: development of the enteric nervous system. Clin Genet 2013; 83(4):307-16. doi: 10.1111/cge.12054

20. Espinosa-Medina I, Jevans B, Boismoreau F, Chettouh Z, Enomoto H, Müller T et al. Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest. Proc Natl Acad Sci USA 2017; 114(45):11980-5. doi: 10.1073/pnas.1710308114

21. Brokhman I, Xu J, Coles B, Razavi R, Engert S, Lickert H,et al. Dual embryonic origin of the mammalian enteric nervous system. Dev Biol 2019; 445(2):256-70. doi:10.1016/j.ydbio.2018.11.014

22. Gammill LS, Gonzalez C, Gu C, Bronner-Fraser M. Guidance of trunk neural crest migration requires neuropilin2/semaphorin 3F signaling. Development 2006; 133(1):99-106. doi:10.1242/dev.02187

23. Escot S, Blavet C, Härtle S, Duband JL, Fournier-Thibault C. Misregulation of SDF1-CXCR4 signaling impairs early cardiac neural crest cell migration leading to conotruncal defects. Circ Res 2013;13(5):505-16. doi:10.1161/CIRCRESAHA.113.301333

24. Wallace AS, Burns AJ. Development of the enteric nervous system, smooth muscle and interstitial cells of  Cajal in the human gastrointestinal tract. Cell Tissue Res 2005; 319(3):367-82. doi:10.1007/s00441-004-1023-2

25. Anderson RB, Stewart AL, Young HM. Phenotypes of neural-crest-derived cells in vagal and sacral pathways. Cell Tissue Res 2006; 323(1):11-25. doi:10.1007/s00441-005-0047-6

26. Nishiyama C, Uesaka T, Manabe T, Yonekura Y, Nagasawa T, Newgreen DF et al. Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system. Nat Neurosci 2012; 15(9):1211-8. doi:10.1038/nn.3184

27. Zuhdi N, Ortega B, Giovannone D, Ra H, Reyes M, Asención V et al. Slit molecules prevent entrance of trunk neural crest cells in developing gut. Int J Dev Neurosci 2015; 41:8-16. doi:10.1016/j.ijdevneu.2014.12.003

28. Burns AJ, Le Douarin NM. Enteric nervous system development: analysis of the selective developmental potentialities of vagal and sacral neural crest cells using quail-chick chimeras. Anat Rec 2001; 262(1):16-28. doi:10.1002/1097-0185(20010101)262:1<16::AIDAR1007>3.0.CO;2-O

29. Shepherd I, Eisen J. Development of the zebrafish enteric nervous system. Methods Cell Biol 2011; 101:143-60. doi:10.1016/B978-0-12-387036-0.00006-2

30. Barlow AJ, Wallace AS, Thapar N, Burns AJ. Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development 2008; 135(9):1681-91. doi:10.1242/dev.017418

31. McKeown SJ, Wallace AS, Anderson RB. Expression and function of cell adhesion molecules during neural crest migration. Dev Biol 2013; 373(2):244-57. doi:10.1016/j.ydbio.2012.10.028

32. Mwizerwa O, Das P, Nagy N, Akbareian SE, Mably JD, Goldstein AM. Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon. Dev Dyn 2011; 240(6):1402-11. doi:10.1002/dvdy.22630

33. Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J et al. Molecular Architecture of the Mouse Nervous System. Cell 2018; 174(4):999-1014. doi:10.1016/j.cell.2018.06.021

34. Lasrado R, Boesmans W, Kleinjung J, Pin C, Bell D, Bhaw L et al. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system. Science 2017; 356(6339):722-6. doi:10.1126/science.aam7511

35. Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J et al. Transcription and Signaling Regulators in Developing Neuronal subtypes of Mouse and Human Enteric Nervous System. Gastroenterology 2018; 154(3):624-36. doi:10.1053/j.gastro.2017.10.005

36. Jiang Y, Liu MT, Gershon MD. Netrins and DCC in the guidance of migrating neural crest-derived cells in the developing bowel and pancreas. Dev Biol 2003; 258(2):364-84. doi:10.1016/s0012-1606(03)00136-2

37. Ratcliffe EM, D’Autréaux F, Gershon MD. Laminin terminates the netrin/DCC mediated attraction of vagal sensory axons. Dev Neurobiol 2008; 68(7):960-71. doi:10.1002/cne.21027

38. Radenkovic G, Radenkovic D, Velickov A. Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells. J Cell Mol Med 2018; 22(2):778-85. doi:10.1111/jcmm.13375

Published
2022/07/09
Section
Review article