The Drosophila Wnt5 protein mediates selective axon fasciculation in the embryonic central nervous system

The Drosophila Wnt5 protein mediates selective axon fasciculation in the embryonic central nervous system
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DOI:
10.1016/j.ydbio.2004.04.034
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发表时间:
2004-08-15
影响因子:
2.7
通讯作者:
Noordermeer, JN
Noordermeer, JN
中科院分区:
生物学3区
文献类型:
--
作者:
Fradkin, LG;van Schie, M;Noordermeer, JN

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决定是否以及在哪里穿过中线,这是中枢神经系统中进化上保守的双侧对称线,是许多新延伸轴突的首要任务。我们发现,Wnt 5,保守的Writ分泌糖蛋白家族的成员,是需要形成的两个中线交叉连合存在于每个果蝇hemisegment的前部。在wnt 5突变胚胎中,跨越两个连合中线的先驱神经元的初始路径发现是正常的;然而,随后的早期跨越中线的轴突分离成两个不同的连合并没有发生。大多数通常穿过前连合中线的跟随轴突未能这样做,保持紧密联系在它们的细胞体附近,或不适当地穿过连合之间的中线。横向和中间纵向通路也未能正确形成,类似地反映了通路解束的早期失败。Wnt 5突变背景中Wnt 5的泛神经表达拯救了连合和纵向缺陷。我们发现,Wnt 5蛋白主要存在于后连合轴突和低水平的前连合和纵向预测。最后,我们证明,最近描述的Wnt 5受体,出轨,在AC神经元中的Wnt 5的转录抑制,有助于这在很大程度上后连合定位的Wnt 5蛋白。(C)2004年爱思唯尔公司All rights reserved.
The decision of whether and where to cross the midline, an evolutionarily conserved line of bilateral symmetry in the central nervous system, is the first task for many newly extending axons. We show that Wnt5, a member of the conserved Writ secreted glycoprotein family, is required for the formation of the anterior of the two midline-crossing commissures present in each Drosophila hemisegment. Initial path finding of pioneering neurons across the midline in both commissures is normal in wnt5 mutant embryos; however, the subsequent separation of the early midline-crossing axons into two distinct commissures does not occur. The majority of the follower axons that normally cross the midline in the anterior commissure fail to do so, remaining tightly associated near their cell bodies, or projecting inappropriately across the midline in between the commissures. The lateral and intermediate longitudinal pathways also fail to form correctly, similarly reflecting earlier failures in pathway defasciculation. Panneural expression of Wnt5 in a wnt5 mutant background rescues both the commissural and longitudinal defects. We show that the Wnt5 protein is predominantly present on posterior commissural axons and at a low level on the anterior commissure and longitudinal projections. Finally, we demonstrate that transcriptional repression of wnt5 in AC neurons by the recently described Wnt5 receptor, Derailed, contributes to this largely posterior commissural localization of Wnt5 protein. (C) 2004 Elsevier Inc. All rights reserved.