Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus.

Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus.
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DOI:
10.1016/j.ydbio.2012.11.025
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发表时间:
2013-02-15
影响因子:
2.7
通讯作者:
Liang JO
Liang JO
中科院分区:
生物学3区
文献类型:
--
作者:
Lu PN;Lund C;Khuansuwan S;Schumann A;Harney-Tolo M;Gamse JT;Liang JO

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大脑左右两侧的差异存在于许多动物物种中。例如,在人类中,左脑半球主要负责语言和工具的使用,而右脑则负责处理空间信息。斑马鱼的上丘脑有明显的左右不对称性,这与左右眼的使用和导航行为有关。在野生型(WT)斑马鱼胚胎中,Nodal途径基因在松果体原基的左侧表达。此后不久,一个松果体旁器官在松果体的左侧形成。松果体旁器官导致左右缰核的基因表达、神经元密度和连接性的差异。在具有开放神经管的胚胎中,例如缺乏Nodal信号传导或细胞粘附蛋白N-钙粘蛋白的胚胎,发育中的上丘脑的左侧和右侧保持彼此分离。我们发现,这些胚胎的大脑变得左异构化:大脑的两侧都发育出左侧特有的形态和基因表达模式。然而,上丘脑发育的其他方面,如特定神经元细胞类型的分化,是完整的。我们提出,在具有封闭神经管的胚胎中存在一种机制,可以防止两侧像左侧一样发育。当上丘脑的两侧彼此相距很远时,这种机制就失效了,这表明它依赖于一种范围有限的信号蛋白。
Differences between the left and right sides of the brain are present in many animal species. For instance, in humans the left cerebral hemisphere is largely responsible for language and tool use and the right for processing spatial information. Zebrafish have prominent left-right asymmetries in their epithalamus that have been associated with differential left and right eye use and navigational behavior. In wild-type (WT) zebrafish embryos, Nodal pathway genes are expressed in the left side of the pineal anlage. Shortly thereafter, a parapineal organ forms to the left of the pineal. The parapineal organ causes differences in gene expression, neuropil density, and connectivity of the left and right habenula nuclei. In embryos that have an open neural tube, such as embryos that are deficient in Nodal signaling or the cell adhesion protein N-cadherin, the left and right sides of the developing epithalamus remain separated from one another. We find that the brains of these embryos become left isomerized: both sides of the brain develop morphology and gene expression patterns that are characteristic of the left side. However, other aspects of epithalamic development, such as differentiation of specific neuronal cell types, are intact. We propose that there is a mechanism in embryos with closed neural tubes that prevents both sides from developing like the left side. This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range.
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