A potential role for somatostatin signaling in regulating retinal neurogenesis.
A potential role for somatostatin signaling in regulating retinal neurogenesis.
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DOI：
10.1038/s41598-021-90554-3
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发表时间：
2021-05-26
影响因子：
4.6
通讯作者：
Blackshaw S
中科院分区：
文献类型：
--
作者：
Weir K;Kim DW;Blackshaw S
神经肽已被报道调节中枢神经系统中的祖细胞增殖和神经发生。然而，这些研究通常是在体外制剂中使用药理学试剂进行的，通常缺乏体内证据来证明它们的发育功能。最近的scRNA-Seq研究发现，多种神经肽及其受体选择性地在胚胎、小鼠和人视网膜的神经源性前体细胞中表达。这包括SSTR2，其配体生长抑素由未成熟的视网膜神经节细胞瞬时表达。通过分析以这些受体为靶点的选择性配体处理的视网膜外植体，我们发现依赖SSTR2的生长抑素信号诱导了适度的、剂量依赖的光感受器生成抑制，同时相应地增加了原代祖细胞的相对比例。这些效应被视网膜外植体的scRNA-Seq分析证实，但在SSTR2缺失的视网膜中被取消。在SSTR2基因缺陷的视网膜中，原代祖细胞或感光细胞前体的相对比例在体内没有变化，但scRNA-Seq分析显示神经源性前体细胞的分化加速。我们的结论是，虽然SSTR2信号可能与其他视网膜神经节细胞来源的分泌因子如Shh一起起到负向调节视网膜神经发生的作用，但它对正常的视网膜发育是必不可少的。
Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a modest, dose-dependent inhibition of photoreceptor generation, while correspondingly increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants but abolished in Sstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed in Sstr2-deficient retinas in vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that, while Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, it is dispensable for normal retinal development.
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