The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons
The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons
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大多数嗅球中间神经元的迁移需要 PROK2/PROKR2 信号通路
DOI：
10.1002/cne.24719
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发表时间：
2019-12-15
影响因子：
2.5
通讯作者：
Yang, Zhengang
中科院分区：
文献类型：
--
作者：
Wen, Yan;Zhang, Zhuangzhi;Yang, Zhengang
侧脑室脑室下区（SVZ）的神经干细胞产生新的中间神经元，其通过吻侧迁移流（RMS）切向迁移到嗅球（OB）。PROK 2（促动素2）和PROKR 2（促动素受体2）信号通路已被鉴定为引起人类卡尔曼综合征，这是一种将性腺功能减退与嗅觉丧失（OB发育缺陷）相关联的发育疾病。然而，SVZ-RMS-OB中PROK 2+和PROKR 2+细胞的身份和性质在很大程度上仍然未知。在这里，我们使用Prok 2 EGFP转基因和Prokr 2LacZ/+敲入小鼠检查了SVZ-RMS-OB中Prok 2和Prokr 2的表达模式。我们的研究结果表明，Prokr 2在SVZ-RMS-OB的有丝分裂后未成熟中间神经元中表达。Prok 2在SVZ中不表达，但在RMS的内侧部分发现了一些PROK 2+细胞;它们不是神经祖细胞或迁移的成神经细胞。在OB中，Prok 2在颗粒细胞和簇状细胞的亚群中表达，但未观察到Prok 2和Prokr 2在OB细胞中的共表达。在Prok 2和Prokr 2突变小鼠中，SVZ-RMS-OB中神经母细胞的严重切向和径向迁移缺陷导致OB中约75%的GABA能中间神经元丢失。这些分析表明，PROK 2/PROKR 2信号传导对于OB中间神经元的切向和径向迁移至关重要。
Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) to the olfactory bulb (OB). The PROK2 (prokineticin 2) and PROKR2 (prokineticin receptor 2) signaling pathway has been identified to cause human Kallmann syndrome, a developmental disease that associates hypogonadism with anosmia (OB developmental defects). However, the identities and properties of PROK2+ and PROKR2+ cells in the SVZ‐RMS‐OB remain largely unknown. Here we examine the expression patterns of Prok2 and Prokr2 in the SVZ‐RMS‐OB using Prok2EGFP transgenic and Prokr2LacZ/+ knockin mice. Our results show that Prokr2 is expressed in postmitotic immature interneurons in the SVZ‐RMS‐OB. Prok2 is not expressed in the SVZ, but a few PROK2+ cells are found in the medial part of the RMS; they are not neural progenitors or migrating neuroblasts. In the OB, Prok2 is expressed in a subset of granule cells and tufted cells, but no coexpression of Prok2 and Prokr2 in the OB cells is observed. In Prok2 and Prokr2 mutant mice, severe tangential and radial migration defects of neuroblasts in the SVZ‐RMS‐OB result in loss of ~75% of GABAergic interneurons in the OB. These analyses demonstrate that PROK2/PROKR2 signaling is crucial for the tangential and radial migration of OB interneurons.