Differentially expressed Drl and Drl-2 play opposing roles in Wnt5 signaling during Drosophila olfactory system development.
Differentially expressed Drl and Drl-2 play opposing roles in Wnt5 signaling during Drosophila olfactory system development.
复制标题
DOI：
10.1523/jneurosci.2821-08.2009
复制
发表时间：
2009-04-15
期刊：
影响因子：
--
通讯作者：
Hama C
中科院分区：
文献类型：
--
作者：
Sakurai M;Aoki T;Yoshikawa S;Santschi LA;Saito H;Endo K;Ishikawa K;Kimura K;Ito K;Thomas JB;Hama C
在果蝇中，嗅觉受体神经元（orn）接收到的气味信息由肾小球处理，肾小球以一种刻板的方式组织在触角叶（AL）中。这种肾小球组织受Wnt5信号的调控。在胚胎中枢，Wnt5信号是由Ryk家族成员Drl受体转导的。然而，在嗅觉系统的发育过程中，它受到Drl的拮抗。在这里，我们发现Drl-2是介导Wnt5信号传导的受体。Drl存在于AL和特定胶质细胞的脑细胞的神经突中，而Drl-2主要存在于生长的ORN轴突亚群中。drl-2突变只会对肾小球模式产生轻微的缺陷，但当它与drl突变结合时，表型会加剧，更接近于Wnt5表型。Wnt5在orn中的过表达可导致肾小球定位异常。这种表型在drl-2突变背景下得到改善，表明drl-2介导Wnt5信号传导。相反，在drl突变体的胶质细胞中强制表达drl -2可以挽救因拮抗drl功能丧失而引起的肾小球表型。因此，Drl-2也可以拮抗Wnt5信号。此外，我们的遗传数据表明，定位于发展中的肾小球的Drl介导Wnt5信号传导。因此，Ryk家族的这两个成员能够执行类似的分子功能，但它们可以在Wnt5信号传导中发挥相反的作用，这取决于它们表达的细胞类型。这些分子协同工作，建立了果蝇的嗅觉回路。
In Drosophila, odor information received by olfactory receptor neurons (ORNs) is processed by glomeruli, which are organized in a stereotypic manner in the antennal lobe (AL). This glomerular organization is regulated by Wnt5 signaling. In the embryonic CNS, Wnt5 signaling is transduced by the Drl receptor, a member of the Ryk family. During development of the olfactory system, however, it is antagonized by Drl. Here, we identify Drl-2 as a receptor mediating Wnt5 signaling. Drl is found in the neurites of brain cells in the AL and specific glia, whereas Drl-2 is predominantly found in subsets of growing ORN axons. A drl-2 mutation produces only mild deficits in glomerular patterning, but when it is combined with a drl mutation, the phenotype is exacerbated and more closely resembles the Wnt5 phenotype. Wnt5 overexpression in ORNs induces aberrant glomeruli positioning. This phenotype is ameliorated in the drl-2 mutant background, indicating that Drl-2 mediates Wnt5 signaling. In contrast, forced expression of Drl-2 in the glia of drl mutants rescues the glomerular phenotype caused by the loss of antagonistic Drl function. Therefore, Drl-2 can also antagonize Wnt5 signaling. Additionally, our genetic data suggest that Drl localized to developing glomeruli mediates Wnt5 signaling. Thus, these two members of the Ryk family are capable of carrying out a similar molecular function, but they can play opposing roles in Wnt5 signaling, depending on the type of cells in which they are expressed. These molecules work cooperatively to establish the olfactory circuitry in Drosophila.