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A Quantitative Cell Migration Assay for Murine Enteric Neural Progenitors
08:26

A Quantitative Cell Migration Assay for Murine Enteric Neural Progenitors

Published on: September 18, 2013

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

Ming Fu1, Yoshiharu Sato, Ariel Lyons-Warren

  • 1Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.

Development (Cambridge, England)
|January 30, 2010
PubMed

Insights

Vitamin A deficiency is a risk factor for Hirschsprung disease, a disorder of the enteric nervous system. Optimizing maternal nutrition may prevent some cases by supporting nerve cell development.

Area of Science:

  • Developmental biology
  • Neuroscience
  • Genetics

Background:

  • Hirschsprung disease (HSCR) results from failed enteric nervous system (ENS) precursor cell migration.
  • Understanding factors influencing ENS development is critical for HSCR research.

Purpose of the Study:

  • To investigate the role of retinoic acid (RA) in ENS precursor cell migration.
  • To determine if vitamin A deficiency impacts HSCR development.

Main Methods:

  • Utilized serum retinol-binding-protein-deficient (Rbp4(-/-)) mice with vitamin A deficiency.
  • Examined the effects of retinoic acid (RA) on GDNF-induced migration, cell polarization, and lamellipodia formation.
  • Assessed the impact of retinoic acid (RA) and Pten levels on ENS precursor migration.

Main Results:

  • Retinoic acid (RA) is essential for GDNF-induced ENS precursor migration, polarization, and lamellipodia formation.
  • Vitamin A depletion in Rbp4(-/-) mice led to distal bowel aganglionosis.
  • Ret heterozygosity exacerbated vitamin A deficiency-induced aganglionosis.
  • RA reduced Pten accumulation, while Pten overexpression inhibited ENS precursor migration.

Conclusions:

  • Vitamin A deficiency acts as a non-genetic risk factor, increasing Hirschsprung disease penetrance and severity.
  • These findings suggest that maternal nutrition optimization could be a preventative strategy for Hirschsprung disease.

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