Ripply1 is a gene encoding a nuclear protein associated with the transcriptional corepressor Groucho. It plays crucial roles in embryonic development, particularly in processes like somitogenesis, the transition from presomitic mesoderm (PSM) to somites, and skeletal myogenesis. It is involved in gene regulatory networks, such as those with Tbx6 and Mesp-b, and is essential for establishing and maintaining proper segmental structures and cell fates [1,2,3,4,5].

In zebrafish, Ripply1 knockdown embryos show deficits in dermomyotome and myotome marker gene expression due to persistent Tbx6 expression, suggesting it promotes myogenesis by terminating Tbx6-dependent inhibition of myogenic maturation [1]. In ripply1-deficient zebrafish embryos, somite boundaries do not form, the characteristic gene expression in the PSM is not properly terminated, and the rostrocaudal polarity in the segmental unit is not maintained [3]. In Ripply1/2-deficient mouse embryos, there are disruptions in the rostro-caudal patterning within a somite, with abnormal expansion of Mesp2 and Tbx6 protein domains [2]. Also, in zebrafish, genetic interaction studies between ripply1/2 and tbx6 show that the relative gene dosage between them is critical for somite formation, and stronger suppression of segmentation gene expression by Ripply is required for proper myogenesis [5].

In conclusion, Ripply1 is essential for proper embryonic development, especially in somitogenesis and myogenesis. Studies using gene-deficient models in zebrafish and mice have revealed its role in regulating key processes during development. Understanding Ripply1 function may provide insights into congenital diseases like congenital scoliosis, where mutations in RIPPLY1 have been identified [6].

References:

1. Windner, Stefanie E, Doris, Rosemarie A, Ferguson, Chantal M, Wardle, Fiona C, Devoto, Stephen H. 2015. Tbx6, Mesp-b and Ripply1 regulate the onset of skeletal myogenesis in zebrafish. In Development (Cambridge, England), 142, 1159-68. doi:10.1242/dev.113431. https://pubmed.ncbi.nlm.nih.gov/25725067/

2. Takahashi, Jun, Ohbayashi, Akiko, Oginuma, Masayuki, Saga, Yumiko, Takada, Shinji. 2010. Analysis of Ripply1/2-deficient mouse embryos reveals a mechanism underlying the rostro-caudal patterning within a somite. In Developmental biology, 342, 134-45. doi:10.1016/j.ydbio.2010.03.015. https://pubmed.ncbi.nlm.nih.gov/20346937/

3. Kawamura, Akinori, Koshida, Sumito, Hijikata, Hiroko, Kondoh, Hisato, Takada, Shinji. . Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites. In Developmental cell, 9, 735-44. doi:. https://pubmed.ncbi.nlm.nih.gov/16326386/

4. Yabe, Taijiro, Uriu, Koichiro, Takada, Shinji. 2023. Ripply suppresses Tbx6 to induce dynamic-to-static conversion in somite segmentation. In Nature communications, 14, 2115. doi:10.1038/s41467-023-37745-w. https://pubmed.ncbi.nlm.nih.gov/37055428/

5. Kinoshita, Hirofumi, Ohgane, Nanae, Fujino, Yuuri, Takada, Shinji, Kawamura, Akinori. 2018. Functional roles of the Ripply-mediated suppression of segmentation gene expression at the anterior presomitic mesoderm in zebrafish. In Mechanisms of development, 152, 21-31. doi:10.1016/j.mod.2018.06.001. https://pubmed.ncbi.nlm.nih.gov/29879477/

6. Yang, Yang, Zhao, Sen, Zhang, Yuanqiang, Zhang, Jianguo, Wu, Nan. 2020. Mutational burden and potential oligogenic model of TBX6-mediated genes in congenital scoliosis. In Molecular genetics & genomic medicine, 8, e1453. doi:10.1002/mgg3.1453. https://pubmed.ncbi.nlm.nih.gov/32815649/