Intrinsic differences among spatially distinct neural crest stem cells in terms of migratory properties, fate determination, and ability to colonize the enteric nervous system

Jack T. Mosher, Kelly J. Yeager, Genevieve M. Kruger, Nancy M. Joseph, Mark E. Hutchin, Andrzej A. Dlugosz, Sean J. Morrison

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

We have systematically examined the developmental potential of neural crest stem cells from the enteric nervous system (gut NCSCs) in vivo to evaluate their potential use in cellular therapy for Hirschsprung disease and to assess differences in the properties of postmigratory NCSCs from different regions of the developing peripheral nervous system (PNS). When transplanted into developing chicks, flow-cytometrically purified gut NCSCs and sciatic nerve NCSCs exhibited intrinsic differences in migratory potential and neurogenic capacity throughout the developing PNS. Most strikingly, gut NCSCs migrated into the developing gut and formed enteric neurons, while sciatic nerve NCSCs failed to migrate into the gut or to make enteric neurons, even when transplanted into the gut wall. Enteric potential is therefore not a general property of NCSCs. Gut NCSCs also formed cholinergic neurons in parasympathetic ganglia, but rarely formed noradrenergic sympathetic neurons or sensory neurons. Supporting the potential for autologous transplants in Hirschsprung disease, we observed that Endothelin receptor B (Ednrb)-deficient gut NCSCs engrafted and formed neurons as efficiently in the Ednrb-deficient hindgut as did wild-type NCSCs. These results demonstrate intrinsic differences in the migratory properties and developmental potentials of regionally distinct NCSCs, indicating that it is critical to match the physiological properties of neural stem cells to the goals of proposed cell therapies.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalDevelopmental Biology
Volume303
Issue number1
DOIs
StatePublished - Mar 1 2007

Keywords

  • Cell therapy
  • Chick embryos
  • Endothelin
  • Enteric nervous system
  • Fate determination
  • Hirschsprung disease
  • Migration
  • Neural crest
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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