Browsing by Author "Shao, Changwei"
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- ceRNA crosstalk mediated by ncRNAs is a novel regulatory mechanism in fish sex determination and differentiationPublication . Tang, Lili; Huang, Fei; You, Wuxin; Poetsch, Ansgar; Nóbrega, Rafael Henrique; Power, Deborah; Zhu, Tengfei; Liu, Kaiqiang; Wang, Hong-Yan; Wang, Qian; Xu, Xiwen; Feng, Bo; Schartl, Manfred; Shao, ChangweiCompeting endogenous RNAs (ceRNAs) are vital regulators of gene networks in mammals. The involvement of noncoding RNAs (ncRNAs) as ceRNA in genotypic sex determination (GSD) and environmental sex determination (ESD) in fish is unknown. The Chinese tongue sole, which has both GSD and ESD mechanisms, was used to map the dynamic expression pattern of ncRNAs and mRNA in gonads during sex determination and differentiation. Transcript expression patterns shift during the sex differentiation phase, and ceRNA modulation occurs through crosstalk of differentially expressed long ncRNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and sex-related genes in fish. Of note was the significant up-regulation of a circRNA from the sex-determining gene dmrt1 (circular RNA dmrt1) and a lncRNA, called AMSDT (which stands for associated with male sex differentiation of tongue sole) in Chinese tongue sole testis. These two ncRNAs both share the same miRNA response elements with gsdf, which has an up-regulated expression when they bind to miRNA cse-miR-196 and concurrent down-regulated female sex-related genes to facilitate testis differentiation. This is the first demonstration in fish that ceRNA crosstalk mediated by ncRNAs modulates sexual development and unveils a novel regulatory mechanism for sex determination and differentiation.
- Exosome delivery to the testes for dmrt1 suppression: a powerful tool for sex-determining gene studiesPublication . Zhu, Tengfei; Kong, Ming; Yu, Yingying; Schartl, Manfred; Power, Deborah; Li, Chen; Ma, Wenxiu; Sun, Yanxu; Li, Shuo; Yue, Bowen; Li, Weijing; Shao, ChangweiExosomes are endosome-derived extracellular vesicles about 100 nm in diameter. They are emerging as prom ising delivery platforms due to their advantages in biocompatibility and engineerability. However, research into and applications for engineered exosomes are still limited to a few areas of medicine in mammals. Here, we expanded the scope of their applications to sex-determining gene studies in early vertebrates. An integrated strategy for constructing the exosome-based delivery system was developed for efficient regulation of dmrt1, which is one of the most widely used sex-determining genes in metazoans. By combining classical methods in molecular biology and the latest technology in bioinformatics, isomiR-124a was identified as a dmrt1 inhibitor and was loaded into exosomes and a testis-targeting peptide was used to modify exosomal surface for efficient delivery. Results showed that isomiR-124a was efficiently delivered to the testes by engineered exosomes and revealed that dmrt1 played important roles in maintaining the regular structure and function of testis in juvenile fish. This is the first de novo development of an exosome-based delivery system applied in the study of sex determining gene, which indicates an attractive prospect for the future applications of engineered exosomes in exploring more extensive biological conundrums.
- The genome and transcriptome of Japanese flounder provide insights into flatfish asymmetryPublication . Shao, Changwei; Bao, Baolong; Xie, Zhiyuan; Chen, Xinye; Li, Bo; Jia, Xiaodong; Yao, Qiulin; Orti, Guillermo; Li, Wenhui; Li, Xihong; Hamre, Kristin; Xu, Juan; Wang, Lei; Chen, Fangyuan; Tian, Yongsheng; Schreiber, Alex M.; Wang, Na; Wei, Fen; Zhang, Jilin; Dong, Zhongdian; Gao, Lei; Gai, Junwei; Sakamoto, Takashi; Mo, Sudong; Chen, Wenjun; Shi, Qiong; Li, Hui; Xiu, Yunji; Li, Yangzhen; Xu, Wenteng; Shi, Zhiyi; Zhang, Guojie; Power, Deborah M.; Wang, Qingyin; Schartl, Manfred; Chen, SonglinFlatfish have the most extreme asymmetric body morphology of vertebrates. During metamorphosis, one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of lopsided body pigmentation(1-5). The evolution of this developmental and physiological innovation remains enigmatic. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. We demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration. The unexpected expression of the visual opsins from the phototransduction pathway in the skin translates illumination differences and generates retinoic acid gradients that underlie the generation of asymmetry. Identifying the genetic underpinning of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, but it also provides insight into the mechanisms that control body shape in vertebrates.