Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures.
Cultures of dissociated foetal and postnatal mouse gut gave rise to neurosphere-like bodies, which contained large numbers of mature neurons and glial cells. In addition to differentiated cells, neurosphere-like bodies included proliferating progenitors which, when cultured at clonal densities, gave rise to colonies containing many of the neuronal subtypes and glial cells present in the mammalian enteric nervous system. These progenitors were also capable of colonising wild-type and aganglionic gut in organ culture and had the potential to generate differentiated progeny that localised within the intrinsic ganglionic plexus. Similar progenitors were also derived from the normoganglionic small intestine of mice with colonic aganglionosis. Our findings establish the feasibility of expanding and isolating early progenitors of the enteric nervous system based on their ability to form distinct neurogenic and gliogenic structures in culture. Furthermore, these experiments provide the rationale for the development of novel approaches to the treatment of congenital megacolon (Hirschsprung's disease) based on the colonisation of the aganglionic gut with progenitors derived from normoganglionic bowel segments.
Bondurand
Nadege
N
Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Natarajan
Dipa
D
Thapar
Nikhil
N
Atkins
Chris
C
Pachnis
Vassilis
V
D000375:Aging; D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics; D017615:Enteric Nervous System / Q000196:embryology*; D005333:Fetus; D007422:Intestines / Q000294:innervation*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009924:Organ Culture Techniques; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D013234:Stem Cells / Q000166:cytology
D029721:Drosophila Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila