PDF(Pubmed)
Abstract：
In the adult mammalian brain, astrocytes are proposed to be the major Sonic Hedgehog (Shh)-responsive cells. However, the sources of the Shh molecule mediating activation of the pathway are still poorly characterized. The present work investigates the distribution and phenotype of cells expressing Shh mRNA in the adult mouse brain. Using single-molecule fluorescent in situ hybridization (smfISH), we report much broader expression of Shh transcripts in almost all brain regions than originally reported. We identify Shh mRNA in HuC/D+ neuronal populations, including GABAergic (glutamic acid decarboxylase 67, Gad67), cholinergic (choline acetyltransferase, ChAT), dopaminergic (tyrosine hydroxylase, TH), nitrergic (neuronal nitric oxide synthase, nNOS), and in a small population of oligodendroglial cells expressing Sox10 and Olig2 mRNA transcription factors. Further analysis of Shh mRNA in cerebral cortical and hypothalamic neurons suggests that Shh is also expressed by glutamatergic neurons. Interestingly, we did not observe substantial Desert Hedgehog and Indian Hedgehog mRNA signals, nor Shh signals in S100β+ astrocytes and Iba1+ microglial cells. Collectively, the present work provides the most robust central map of Shh-expressing cells to date and underscores the importance of nitrergic neurons in regulating Shh availability to brain cells. Thus, our study provides a framework for future experiments aimed at better understanding of the functions of Shh signaling in the brain in normal and pathological states, and the characterization of novel regulatory mechanisms of the signaling pathway.
摘要：
在成年哺乳动物的大脑中，星形胶质细胞被认为是主要的SonicHedgehog（Shh）响应细胞。然而,介导途径激活的Shh分子的来源仍然缺乏表征。本工作研究了成年小鼠大脑中表达ShhmRNA的细胞的分布和表型。使用单分子荧光原位杂交（smfISH），我们报道了Shh转录本在几乎所有大脑区域的表达比最初报道的要广泛得多。我们鉴定了HuC/D+神经元群体中的ShhmRNA，包括GABA能（谷氨酸脱羧酶67，Gad67），胆碱能（胆碱乙酰转移酶，Chat),多巴胺能（酪氨酸羟化酶，TH),硝态氮（神经元型一氧化氮合酶，nNOS),以及表达Sox10和Olig2mRNA转录因子的少量少突胶质细胞。对大脑皮层和下丘脑神经元中ShhmRNA的进一步分析表明，谷氨酸能神经元也表达Shh。有趣的是,我们没有观察到大量的沙漠刺猬和印度刺猬mRNA信号，S100β+星形胶质细胞和Iba1+小胶质细胞中的Shh信号。总的来说，目前的工作提供了迄今为止最强大的Shh表达细胞的中央图谱，并强调了硝能神经元在调节Shh对脑细胞的可用性方面的重要性。因此，我们的研究为未来的实验提供了一个框架，旨在更好地了解正常和病理状态下大脑中Shh信号的功能，以及信号通路新型调控机制的表征。
