Neural crest regionalisation for enteric nervous system formation: Implications for Hirschsprung's disease and stem cell therapy

Midbrain, hindbrain and vagal neural crest (NC) produced abundant enteric nervous system (ENS) in co-grafted aneural hindgut and midgut, using chick–quail chorio-allantoic membrane grafts, forming complete myenteric and submucosal plexuses. This ability dropped suddenly in cervical and thoracic NC l...

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Bibliographic Details
Published in:Developmental biology 2010-03, Vol.339 (2), p.280-294
Main Authors: Zhang, Dongcheng, Brinas, Inigo M., Binder, Benjamin J., Landman, Kerry A., Newgreen, Donald F.
Format: Article
Language:English
Subjects:
Animals
Body Patterning
Cell Differentiation
Cell Proliferation
Chick Embryo
Enteric nervous system
Enteric Nervous System - embryology
Hirschsprung Disease - embryology
Hirschsprung Disease - therapy
Intestine
Neural crest
Neural Crest - cytology
Neural Crest - embryology
Neural Crest - transplantation
Positional information
Stem Cell Transplantation
Stem Cells - cytology
Vagus Nerve - cytology
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Summary:Midbrain, hindbrain and vagal neural crest (NC) produced abundant enteric nervous system (ENS) in co-grafted aneural hindgut and midgut, using chick–quail chorio-allantoic membrane grafts, forming complete myenteric and submucosal plexuses. This ability dropped suddenly in cervical and thoracic NC levels, furnishing an incomplete ENS in one or both plexuses. Typically, one plexus was favoured over the other. This deficiency was not caused by lower initial trunk NC number, yet overloading the initial number decreased the deficiency. No qualitative difference in neuronal and glial differentiation between cranial and trunk levels was observed. All levels formed HuC/D+ve, NOS+ve, ChAT+ve, and TH-ve enteric neurons with SoxE+ve, GFAP+ve, and BFABP+ve glial cells. We mathematically modelled a proliferative difference between NC populations, with a plexus preference hierarchy, in the context of intestinal growth. High proliferation achieved an outcome similar to cranial NC, while low proliferation described the trunk NC outcome of incomplete primary plexus and even more deficient secondary plexus. We conclude that cranial NC, relative to trunk NC, has a positionally-determined proliferation advantage favouring ENS formation. This has important implications for proposed NC stem cell therapy for Hirschsprung's disease, since such cells may need to be optimised for positional identity.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2009.12.014