Protocadherin-19 is essential for early steps in brain morphogenesis

Protocadherin-19 is essential for early steps in brain morphogenesis
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DOI:
10.1016/j.ydbio.2009.07.008
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发表时间:
2009-10-01
影响因子:
2.7
通讯作者:
Jontes, James D.
Jontes, James D.
中科院分区:
生物学3区
文献类型:
--
作者:
Emond, Michelle R.;Biswas, Sayantanee;Jontes, James D.

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脑形态发生的最早阶段之一是在神经胚形成期间建立神经管。虽然一些负责神经形成的细胞机制已在许多脊椎动物物种中描述,但其潜在的分子过程尚未完全了解。我们已经确定了原钙粘蛋白19,钙粘蛋白超家族的成员,这是在前神经板表达,是大脑形态发生所需的斑马鱼同源物。用反义吗啉代寡核苷酸干扰原钙粘蛋白-19的功能导致早期脑形态发生的严重破坏。尽管这些显着的影响神经形成,轴向图案的神经管出现正常,作为评估的otx 2,pax2.1和krox 20的原位杂交。在体内2-光子时移显微镜发育早期胚胎的表征表明,观察到的破坏形态的结果从逮捕前神经板的细胞会聚。这些结果提供了原钙粘蛋白-19的第一个功能数据,证明了在早期大脑发育中的重要作用。(C)2009 Elsevier Inc. All rights reserved.
One of the earliest stages of brain morphogenesis is the establishment of the neural tube during neurulation. While some of the cellular mechanisms responsible for neurulation have been described in a number of vertebrate species, the underlying molecular processes are not fully understood. We have identified the zebrafish homolog of protocadherin-19, a member of the cadherin superfamily, which is expressed in the anterior neural plate and is required for brain morphogenesis. Interference with Protocadherin-19 function with antisense morpholino oligonucleotides leads to a severe disruption in early brain morphogenesis. Despite these pronounced effects on neurulation, axial patterning of the neural tube appears normal, as assessed by in situ hybridization for otx2, pax2.1 and krox20. Characterization of embryos early in development by in vivo 2-photon timelapse microscopy reveals that the observed disruption of morphogenesis results from an arrest of cell convergence in the anterior neural plate. These results provide the first functional data for protocadherin-19, demonstrating an essential role in early brain development. (C) 2009 Elsevier Inc. All rights reserved.