PDF(Pubmed)
Abstract：
Haploinsufficiency of the PRR12 gene is implicated in a human neuro-ocular syndrome. Although identified as a nuclear protein highly expressed in the embryonic mouse brain, PRR12 molecular function remains elusive. This study explores the spatio-temporal expression of zebrafish PRR12 co-orthologs, prr12a and prr12b, as a first step to elucidate their function. In silico analysis reveals high evolutionary conservation in the DNA-interacting domains for both orthologs, with significant syntenic conservation observed for the prr12b locus. In situ hybridization and RT-qPCR analyses on zebrafish embryos and larvae reveal distinct expression patterns: prr12a is expressed early in zygotic development, mainly in the central nervous system, while prr12b expression initiates during gastrulation, localizing later to dopaminergic telencephalic and diencephalic cell clusters. Both transcripts are enriched in the ganglion cell and inner neural layers of the 72 hpf retina, with prr12b widely distributed in the ciliary marginal zone. In the adult brain, prr12a and prr12b are found in the cerebellum, amygdala and ventral telencephalon, which represent the main areas affected in autistic patients. Overall, this study suggests PRR12\'s potential involvement in eye and brain development, laying the groundwork for further investigations into PRR12-related neurobehavioral disorders.
摘要：
PRR12基因的单倍功能不全与人类神经眼综合征有关。尽管被鉴定为在胚胎小鼠大脑中高度表达的核蛋白，PRR12分子功能仍然难以捉摸。本研究探讨了斑马鱼PRR12同源物的时空表达，prr12a和prr12b，作为阐明其功能的第一步。计算机模拟分析揭示了两种直系同源物的DNA相互作用域的高度进化保守性，在prr12b基因座上观察到显着的同势保守性。斑马鱼胚胎和幼虫的原位杂交和RT-qPCR分析揭示了不同的表达模式：prr12a在合子发育早期表达，主要在中枢神经系统，而prr12b表达在原肠胚形成过程中开始，后来定位到多巴胺能端脑和间脑细胞簇。两种转录本都富集在72hpf视网膜的神经节细胞和内部神经层中，prr12b广泛分布在睫状边缘区。在成年人的大脑中，prr12a和prr12b在小脑中发现，杏仁核和腹侧端脑，这代表了自闭症患者受影响的主要领域。总的来说,这项研究表明，PRR12可能参与眼睛和大脑发育，为PRR12相关神经行为障碍的进一步研究奠定基础。
