Thursday, October 28, 2010

Vitamin A Deficiency and Hirschsprung Disease

Dr. Robert Heuckeroth and his team and Washington University recently published more results on the link between maternal Vitamin A Deficiency and Hirschsprung Disease. It underscores the importance of maternal vitamin A nutrition for preventing the diease penetrance and expressitivity:
Ming Fu, Yoshiharu Sato, Ariel Lyons-Warren, Bin Zhang, Maureen A. Kane, Joseph L. Napoli and Robert O. Heuckeroth. Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Development 137, 631-640 (2010) doi:10.1242/dev.040550.
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 retinolbinding-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.

By the way, the lab has been an ongoing consumer of our Ret Antibody and referenced use of this antibody in the publication.

Image: E12.5 mouse mid-gut slices were cultured to allow crest-derived cells to migrate onto the dish in response to GDNF. Cultures were maintained for 16 hours without added retinoic acid.

Related Reagents:

Ret (C-Terminus Fused)

Ret-Fluorescein Labeled

Ret-Allophycocyanin Labeled

Ret-Phycoerythrin Labeled

Neurotrophins and Growth Factor Antibodies

Neurotrophins-Neuron/Glial Marker
Recombinant Proteins

Neuron/Glial Markers

Stem Cell Research Reagents

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