Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation
Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation
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DOI：
10.1242/dev.040550
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发表时间：
2010-02-15
期刊：
影响因子：
4.6
通讯作者：
Heuckeroth, Robert O.
中科院分区：
文献类型：
--
作者：
Fu, Ming;Sato, Yoshiharu;Heuckeroth, Robert O.
先天性巨结肠是一种严重的肠神经系统（ENS）发育障碍，其原因是ENS前体细胞不能迁移到远端肠道。我们现在证明，视黄酸（RA）是至关重要的GDNF诱导的ENS前体迁移，细胞极化和板状伪足的形成，维生素A消耗导致远端肠无神经节细胞在血清视黄醇结合蛋白缺陷（Rbp 4（-/-））小鼠。Ret杂合性增加Rbp 4（-/-）动物中维生素A缺乏诱导的远端肠无神经节细胞症的发生率和严重程度此外，RA减少迁移细胞中磷酸酶和张力蛋白同源物（Pten）的积累，而Pten过表达减缓ENS前体迁移。总的来说，这些数据支持维生素A缺乏是一个非遗传性风险因素，增加先天性巨结肠症的发病率和表现力的假设，这表明一些先天性巨结肠症的病例可能是可以通过优化母体营养来预防的。
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.