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

M Fu, Y Sato, A Lyons-Warren, B Zhang… - …, 2010 - journals.biologists.com
M Fu, Y Sato, A Lyons-Warren, B Zhang, MA Kane, JL Napoli, RO Heuckeroth
Development, 2010journals.biologists.com
Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development
caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate
that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization
and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis
in serum retinol-binding-protein-deficient (Rbp4–/–) mice. Ret heterozygosity increases the
incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in …
Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinol-binding-protein-deficient (Rbp4–/–) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4–/– animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition.
journals.biologists.com