Young laboratory: Development of the enteric nervous system

Research Overview

Within the wall of the gut, there is an extensive nervous system, the enteric nervous system, which plays an essential role in the control of gut motility.

During development, enteric neurons arise from neural crest cells that emigrate from the caudal hindbrain and migrate into and along the developing gut.  Enteric neural crest cells are thought to migrate further than any other embryonic cell population.

Our research is focused on the mechanisms controlling the development of the enteric nervous system and the potential of cell therapy for treating diseases of the enteric nervous system.

Staff

Dr Sonja McKeown, Senior Research Officer
Dr Lincon Stamp, Senior Research Officer
Ms Annette Bergner, Research Assistant
Ms Rachel Gwynne, Research Assistant
Ms Jan Morgan, Technical Officer
Ms Mitra Mohsenipour, Research Assistant

Collaborators

Professor Joel Bornstein, Department of Physiology, University of Melbourne
Professor John Furness, Department of Anatomy and Neuroscience, University of Melbourne
Professor Hideki Enomoto, Kobe University School of Medicine
Professor Andrew Allen, Department of Physiology, University of Melbourne

Funding

NHMRC Project Grant APP1079234: Young HM, Stamp LA, Bornstein JC. Cell therapies for enteric neuropathies - the essential next step. 2015-2017. $645K

ARC Discovery Project DP150103709: Young HM. Neural migration: Which cells advance and which stay behind? 2015-2017. $421K

NHMRC Project Grant APP1047953: Young HM & McKeown SJ. Role of KBP and spontaneous activity in the development of the enteric neurons. 2013-2015 (extended until 31.12.16). $579K

NHMRC Project Grant APP1043397: Young HM & McKeown SJ. Manipulation of progenitors prior to transplantation to enhance the generation of enteric neurons. 2013-2015 (extended to 31.12.16). $587K

NHMRC Senior Research Fellowship APP1002506: Young HM, Development of neurons in the gut. 2011-2015.

NHMRC Project Grant APP1063822: Anderson CR & Young HM. Differentiation and fate in developing sympathetic ganglia. 2014-2016. $333K

ARC Discovery Project DP130101569: Bornstein JC, Young HM, Vanden Berghe P. Wiring the gut's nervous system: Formation and maturation of synapses. 2013-2015. $510K

Research Publications

  • Hao MM, Boesmans W Van Den Abbeel V, Jennings EA, Bornstein JC, Young HM, Vanden Berghe P. Early emergence of neural activity in the developing mouse enteric nervous system. J Neurosci 2011; 31: 15352-15361.
  • Young HM, Newgreen DF, Enomoto H. Development of the enteric nervous system. In: Physiology of the Gastrointestinal Tract, Fifth edition. Ed: L. Johnson, Oxford: Academic Press, 2012: pp 475-488. ISBN: 978-0-12-382026-6
  • Foong JPP, Nguyen T. Furness JB, Bornstein JC, Young HM. Myenteric neurons of the mouse small intestine undergo significant electrophysiological and morphological changes during post-natal development. J Physio 2012; 590: 2375-2390. This article was the subject of a commentary by the journal, see J Physiol590: 2185-2186
  • Hao MM, Lomax AE, McKeown SJ, Reid CA, YOUNG HM, Bornsteing JC. Early development of electrical excitability in the mouse enteric nervous system. J Neurosci 2012; 32: 10949-1-960.
  • Nishiyama C, Uesake T, Manabe T, Yonekura Y, NAGASAWA T, Newgreen DF, Young HM, Enmoto H. Trans-mesenteric neural crest cells are the principal source for the colonic enteric nervous system. Nat Neurosci 2012 Sep; 15(9): 1211-8.
  • McKeown SG, Stamp L, Hao MM, Young HM. Hirschsprung disease: a developmental disorder of the enteric nervous system. WIREs Dev. Biol. 2013; 2: 113-29.(2013 doi: 10.1002/wdev.57
  • Obermayr F, Hotta R, Enomoto H, Young HM. Development and developmental disorders of the enteric nervous system. >Nature Rev Gastro Hepatol 2013; 10: 43-57
  • Hotta R, Stamp LA, Foong JPP, Bergner AJ, McConnell SN, Anderson RB, Enomoto H, Newgreen DF, Obermayr F, Furness JB, Young HM. Transplanted progenitors generate functional enteric neurons in the postnatal colon. J Clin Invest 2013; 123: 1182-91.
  • Gonsalvez DG, Cane KN, Landman KA, Enomoto H, Young HM, Anderson CR. . Proliferation and cell cycle dynamics in the developing stellate ganglion. J Neurosci 2013; 33: 5969-5979.
  • Hao MM, Bornstein JC, Vanden Berghe P, Lomax AE, Young HM, Foong JPP. The emergence of neural activity and its role in the development of the enteric nervous system. Dev Biol 2013; 382: 365-374.
  • Young HM, Beckett EA, Bornstein JC, Jadcherla S. . Development of gut motility. In: Pediatric Neurogastroenterology: Gastrointestinal motility and functional disorders in children, Ed C. Faure, C. Di Lorenzo and N. Thapar, Humana Press, 2013, pp 23-35.
  • Obermayr F, Stamp LA, Anderson CR, Young HM.  Genetic fate-mapping of tyrosine hydroxylase-expressing cells in the enteric nervous system. Neurogastro Motil 2013; 25:e 283-e291.
  • Hao MM, Bornstein JC, Young HM.  Development of myenteric cholinergic neurons in ChAT-Cre;R26R-YFP mice. J Comp Neurol 2013; 521: 3358-3370.
  • Bergner AJ, Stamp LA, Gonsalvez DG, Allison MB, Olson DP, Myers MG Jr, Anderson CR, Young HM. Birthdating of different myenteric neuron subtypes in the small intestine of the mouse. J Comp Neurol 2014; 522: 514-527.
  • Young HM*, Bergner AJ, Simpson MJ, McKeown SJ, Hao MM, Anderson CR, Enomoto H.  Colonizing while migrating: How do individual enteric neural crest cell behave? BMC Biol 2014; 12:23.  *corresponding author
  • Findlay Q, Yap K, Bergner AJ, Young HM*, Stano LA.*  Enteric neural progenitors are more efficient than brain-derived progenitors at generating neurons in the colon. Am J Physiol Gastrointest Liver Physiol 2014; 307: G741-8. *equal corresponding authors
  • Gonsalvez DG, Fong MLY, Cane KN, Stamp LA, Young HM, Anderson CR.  Different neural crest populations exhibit diverse proliferative behaviors. Dev Neurobiol 2015; 75: 287-301
  • Young, HM. All is not normal in "normoganglionic" bowel regions of Hirschsprung-disease model mice. Cell Mol Gastro Hepatol 2015; 1: 4-5.
  • Foong JPP, Hirst CS, Hao MM, McKeown SJ, Boesmans W, Young HM*, Bornstein JC*, Vanden Berghe P*. Changes in nicotinic neurotransmission during enteric nervous system development. J Neurosci 2015; 35: 7106-7115. *equal senior authors
  • Hirst CS, Foong JPP, Stamp LA, Fegan E, Dent S, Cooper EC, Lomax AE, Anderson CR, Bornstein JC, Young HM*, McKeown SJ*. Ion channel expression in the developing enteric nervous system. PLOS ONE 2015; 10(3): e0123436. *equal corresponding authors
  • Chan WH, Gonsalvez DG, Young HM, Southard-Smith EM, Cane KN, Anderson CR. Differences in CART expression and cell cycle behavior discriminate sympathetic neuroblast from chromaffin cell lineages in mouse sympathoadrenal cells. Dev Neurobiol 2015; in press; accepted 14.05.15).
  • Chan WH, Stamp LA, Hirst CS, McKeown SJ, Anderson CR, Young HM.  Development of the autonomic nervous system. Reviews in Cell Biology and Molecular Medicine 2015; in press, accepted 14.05.15).
  • Stamp LA, Obermayr F, Pontell L, Young HM, Xie D, Croaker D, Song Z-M, Furness JB.  Surgical intervention to rescue Hirschsprung disease in a rat model. J Neurogastro Motil 2015; 21: 552-559.
  • Young HM, Stamp LA, Hofstra RMW.  Hirschsprung Disease and Activation of Hedgehog Signaling via GLI1-3 mutations. Gastroenterology 2015; in press.
  • Beckett EA, Young HM, Bornstein JC, Jadcherla S. Development of gut motility. In: Pediatric Neurogastroenterology: Gastrointestinal motility and functional disorders in children, Ed C. Faure, C. Di Lorenzo and N. Thapar, Humana Press, 2016; in press.