PDF(Pubmed)
Abstract：
Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy-associated mossy fiber (MF) sprouting in the adult hippocampus and asked which cell surface molecules define its target specificity. Using single-cell RNAseq data, we found lack and expression of Pcdh11x in non-sprouting and sprouting neurons respectively. Subsequently, we used CRISPR/Cas9 genome editing to disrupt the Pcdh11x gene and characterized its consequences on sprouting. Although MF sprouting still developed, its target specificity was altered. New synapses were frequently formed on granule cell somata in addition to dendrites. Our findings shed light onto a key molecular determinant of target specificity in MF sprouting and contribute to understanding the molecular mechanism of adult brain rewiring.
摘要：
电路形成是发育中的大脑的决定性特征。然而,多条证据表明，电路的形成也可以发生在成年人身上，其机制仍然知之甚少。这里,我们调查了成年海马中癫痫相关苔藓纤维(MF)的发芽,并询问哪些细胞表面分子定义了其靶特异性.使用单细胞RNAseq数据，我们发现Pcdh11x分别在非发芽和发芽神经元中缺乏和表达。随后，我们使用CRISPR/Cas9基因组编辑来破坏Pcdh11x基因，并表征其对发芽的影响。尽管MF发芽仍在发展，其靶特异性改变。除树突外，还经常在颗粒细胞躯体上形成新的突触。我们的发现揭示了MF发芽中靶标特异性的关键分子决定因素，并有助于理解成人大脑重新布线的分子机制。
