EMT is the major target for okadaic acid-suppressed the development of neural crest cells in chick embryo
EMT is the major target for okadaic acid-suppressed the development of neural crest cells in chick embryo
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EMT是冈田酸抑制鸡胚神经嵴细胞发育的主要靶点
DOI：
10.1016/j.ecoenv.2019.05.015
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发表时间：
2019
影响因子：
6.8
通讯作者：
Yang Wei dong
中科院分区：
文献类型：
--
作者：
Jiao Yu hu;Liu Meng;Wang Guang;Li Hong ye;Liu Jie sheng;Yang Xuesong;Yang Wei dong
冈田酸（okadaic acid，OA）是一种主要的海洋藻毒素，通过特异性抑制磷酸酶（PP 1和PP 2A）而引起贝类中毒。已经显示同位素标记的-OA可以穿过小鼠的胎盘屏障。然而，OA暴露如何影响神经嵴细胞（NCC）的形成，特别是在早期胚胎发育中的颅NCC，仍然不清楚。在这里，我们探讨了OA暴露对神经嵴细胞的产生在胚胎发育过程中使用经典的鸡胚模型的影响。我们发现，OA暴露在100 nM（80.5 μg/L）可导致发育中的鸡胚颅面骨缺损，并延迟早期鸡胚的发育。HNK-1、Pax 7和Ap-2α的免疫荧光染色表明，OA暴露抑制了颅NCC的产生。Ap-2α/PHIS 3或Pax 7/c-Caspase 3免疫荧光双标显示OA抑制NCC增殖和凋亡。Msx 1和BMP 4在鸡胚神经管发育过程中表达下调，可能与抑制神经细胞生成有关。我们还发现，EMT相关的粘附分子，如钙粘蛋白6 B（Cad 6 B）和E-钙粘蛋白的表达，改变后OA暴露。总之，OA暴露对胚胎神经嵴细胞的发育产生负面影响，这反过来又可能导致颅骨畸形。
As a main marine phycotoxin, okadaic acid (OA) is mainly responsible for diarrheic shellfish poisoning (DSP), through specifically inhibiting phosphatase (PP1 and PP2A). It has been shown that isotope labelled-OA could cross the placental barrier in mice. However, it remains obscure how OA exposure could affect the formation of neural crest cells (NCCs), especially cranial NCCs in early embryo development. Here, we explored the effects of OA exposure on the generation of neural crest cells during embryonic development using the classic chick embryo model. We found that OA exposure at 100 nM (80.5 μg/L) could cause craniofacial bone defects in the developing chick embryo and delay the development of early chick embryos. Immunofluorescent staining of HNK-1, Pax7, and Ap-2α demonstrated that cranial NCC generation was inhibited by OA exposure. Double immunofluorescent staining with Ap-2α/PHIS3 or Pax7/c-Caspase3 manifested that both NCC proliferation and apoptosis were restrained by OA exposure. Furthermore, the expression ofMsx1andBMP4were down-regulated in the developing chick embryonic neural tubes, which could contribute the inhibitive production of NCCs. We also discovered that expression of EMT-related adhesion molecules, such as Cadherin 6B (Cad6B) and E-cadherin, was altered following OA exposure. In sum, OA exposure negatively affected the development of embryonic neural crest cells, which in turn might result in cranial bone malformation.