Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro
Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro
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DOI：
10.1002/dvdy.10303
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发表时间：
2003-06-01
影响因子：
2.5
通讯作者：
Gittenberger-de Groot, AC
中科院分区：
文献类型：
--
作者：
Boot, MJ;Steegers-Theunissen, RPM;Gittenberger-de Groot, AC
已证明在受孕前后补充叶酸对预防后代神经管缺陷、口面裂和圆锥动脉干心脏缺陷具有有益作用。叶酸缺乏会导致同型半胱氨酸积累。同型半胱氨酸水平升高与神经管缺陷有关。我们在体外研究了神经上皮细胞以及颅神经嵴细胞和心脏神经嵴细胞的行为。在添加叶酸和/或同型半胱氨酸后，将神经管外植体在培养基中培养24小时和48小时。添加叶酸可促进神经上皮细胞的增殖，并增加神经嵴细胞向神经细胞和平滑肌细胞的分化。添加同型半胱氨酸可增加神经嵴细胞从神经管的增殖和迁移，并抑制神经嵴细胞的分化。我们的研究结果表明，由叶酸缺乏和高同型半胱氨酸血症引起的神经管缺陷是由于神经上皮细胞向神经嵴细胞转化增加所致。这种转化增加导致神经管中神经上皮细胞短缺。在高同型半胱氨酸浓度存在的情况下，神经嵴细胞的异常分化解释了口面和圆锥动脉干发育的缺陷。我们的研究结果支持叶酸和同型半胱氨酸在神经管缺陷以及神经嵴相关心脏畸形发育中起关键作用。《发育动力学》2003年第227卷第301 - 308页。（C）2003年威利 - 利斯公司。
The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to neural tube defects. We studied the behavior of neuroepithelial cells and cranial and cardiac neural crest cells in vitro. Neural tube explants were cultured for 24 and 48 hr in medium after addition of folic acid and/or homocysteine. Folic acid addition increased neuroepithelial cell outgrowth and increased neural crest cell differentiation into nerve and smooth muscle cells. Addition of homocysteine increased neural crest cell outgrowth and migration from the neural tube and inhibited neural crest cell differentiation. Our findings suggest that neural tube defects caused by folate deficiency and hyperhomocysteinemia develop due to increased neuroepithelial to neural crest cell transformation. This increased transformation leads to a shortage of neuroepithelial cells in the neural tube. Defects in orofacial and conotruncal development are explained by abnormal differentiation of neural crest cells in the presence of high homocysteine concentrations. Our findings supports a critical role for folic acid and homocysteine in the development of neural tube defects and neural crest related heart malformations. Developmental Dynamics 227.301-308, 2003. (C) 2003 Wiley-Liss, Inc.