转录抑制因子RP58与人类1q43-q44染色体缺失综合征密切相关，在小鼠中的研究表明RP58也调控小鼠胚胎晚期脑部发育，在成纤维诱导神经细胞过程中该基因高度表达，并起到关键作用，但目前对RP58是否调控早期神经系统发育还知之甚少。我们用视黄酸拮抗剂BMS453处理非洲爪蛙早期胚胎后发现RP58是视黄酸潜在靶基因。RP58主要表达于爪蛙神经胚尾端，尾芽胚阶段其表达扩展到头端。初步功能敲减和过表达分析提示，RP58参与调控爪蛙早期神经系统眼、脑、神经嵴等的发育。本项目拟在前期工作基础上，通过建立热带爪蛙RP58敲除模型，研究在胚胎发育早期RP58与视黄酸、组蛋白乙酰化的关系；通过原位杂交、RNA-seq、ChIP-seq等方法系统地揭示RP58调控爪蛙早期神经系统发育的功能及其作用机制，本项目的实施将有助于全面认识1q43-q44染色体缺失综合征的发病机理，为神经细胞的体外成熟诱导提供参考。

Transcription repressor RP58 is closely associated with human chromosome 1q43-q44 deletion syndrome. Studies in mice indicated that RP58 also regulates late stage mouse embryonic brain development. RP58 is highly expressed during fibroblasts induced neuron differentiation, and plays a key role in this process. However, little is known about whether RP58 is involved in the regulation of early stage embryonic neural development. We successfully identified RP58 as a potential RA target gene by treating gastrulating Xenopus embryos with BMS453, an RA antagonist. RP58 is mainly expressed at the posterior part of Xenopus neurulae. The expression spreads to the head during the tail bud stage of development. Our preliminary data on morpholino-mediated knockdown or overexpression of RP58 in Xenopus embryos suggests that RP58 may regulate early stage Xenopus neural development. Here, we propose to further investigate the role of RP58 in early phases of Xenopus neural development including eyes, brain and neural crest. We will generate Xenopus tropicalis RP58 knockout model to characterize the mechanism of RP58 in neural development. First, we will test whether RP58 functions through RA signaling and/or histone acetylation. Second, we will study the mechanism of RP58 in early neural development by using in situ hybridization and qPCR. Finally, we will identify RP58 target genes in early embryoes by RNA-seq, ChIP-seq etc. Our study may help understand the disease development of human chromosome 1q43-q44 deletion syndrome, and may provide potential targets for in vitro reprogramming of fibroblasts into neurons.