Abstract:
:The enteric nervous system (ENS) forms from the neural crest-derived precursors that colonize the bowel before differentiating into a network of neurons and glia that control intestinal function. Retinoids are essential for normal ENS development, but the role of retinoic acid (RA) metabolism in development remains incompletely understood. Because RA is produced locally in the tissues where it acts by stimulating RAR and RXR receptors, RA signaling during development is absolutely dependent on the rate of RA synthesis and degradation. RA is produced by three different enzymes called retinaldehyde dehydrogenases (RALDH1, RALDH2 and RALDH3) that are all expressed in the developing bowel. To determine the relative importance of these enzymes for ENS development, we analyzed whole mount preparations of adult (8-12-week old) myenteric and submucosal plexus stained with NADPH diaphorase (neurons and neurites), anti-TuJ1 (neurons and neurites), anti-HuC/HuD (neurons), and anti-S100β (glia) in an allelic series of mice with mutations in Raldh1, Raldh2, and Raldh3. We found that Raldh1-/-, Raldh2+/-, Raldh3+/- (R1(KO)R2(Het)R3(Het)) mutant mice had a reduced colon myenteric neuron density, reduced colon myenteric neuron to glia ratio, reduced colon submucosal neuron density, and increased colon myenteric fibers per neuron when compared to the wild type (WT; Raldh1WT, Raldh2WT, Raldh3WT) mice. These defects are unlikely to be due to defective ENS precursor migration since R1(KO)R2(Het)R3(KO) mice had increased enteric neuron progenitor migration into the distal colon compared to WT during development. RALDH mutant mice also have reduced contractility in the colon compared to WT mice. These data suggest that RALDH1, RALDH2 and RALDH3 each contribute to ENS development and function.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Wright-Jin EC,Grider JR,Duester G,Heuckeroth ROdoi
10.1016/j.ydbio.2013.06.021subject
Has Abstractpub_date
2013-09-01 00:00:00pages
28-37issue
1eissn
0012-1606issn
1095-564Xpii
S0012-1606(13)00338-2journal_volume
381pub_type
杂志文章abstract::The canonical, beta-catenin-dependent Wnt pathway is a crucial player in the early events of Xenopus development. Dorsal axis formation and mesoderm patterning are accepted effects of this pathway, but the regulation of expression of genes involved in mesoderm specification is not. This conclusion is based largely on ...
journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
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journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
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