X-Linked Retinitis Pigmentosa 2 Is a Novel Maternal-Effect Gene Required for Left-Right Asymmetry in Zebrafish1

Abstract

Retinitis pigmentosa 2 (RP2) gene is responsible for up to 20% of X-linked retinitis pigmentosa, a severe heterogeneous genetic disorder resulting in progressive retinal degeneration in humans. In vertebrates, several bodies of evidence have clearly established the role of Rp2 protein in cilia genesis and/or function. Unexpectedly, some observations in zebrafish have suggested the oocyte-predominant expression of the rp2 gene, a typical feature of maternal-effect genes. In the present study, we investigate the maternal inheritance of rp2 gene products in zebrafish eggs in order to address whether rp2 could be a novel maternal-effect gene required for normal development. Although both rp2 mRNA and corresponding protein are expressed during oogenesis, rp2 mRNA is maternally inherited, in contrast to Rp2 protein. A knockdown of the protein transcribed from both rp2 maternal and zygotic mRNA results in delayed epiboly and severe developmental defects, including eye malformations, that were not observed when only the protein from zygotic origin was knocked down. Moreover, the knockdown of maternal and zygotic Rp2 revealed a high incidence of left-right asymmetry establishment defects compared to only zygotic knockdown. Here we show that rp2 is a novel maternal-effect gene exclusively expressed in oocytes within the zebrafish ovary and demonstrate that maternal rp2 mRNA is essential for successful embryonic development and thus contributes to egg developmental competence. Our observations also reveal that Rp2 protein translated from maternal mRNA is important to allow normal heart loop formation, thus providing evidence of a direct maternal contribution to left-right asymmetry establishment.

Maternal investment in fish oocytes and eggs: The molecular cargo and its contributions to fertility and early development

“…Great advancement in identifying mRNAs with functions in developing oocytes was made by screening maternal-effect mutations in zebrafish and medaka, which resulted in a relatively large number of phenotypic mutants, but in many cases their molecular identity remains unknown. Additional information was gained from gene knockdown studies based on microinjection of antisense morpholino oligonucleotides (Tables 1 and 2; Dosch et al, 2004;Wagner et al, 2004 andreviews: Lyman-Gingerich andAbrams and Mullins, 2009;Marlow, 2010;Traverso et al, 2012;Bouleau et al, 2014;Nishimura and Tanaka, 2014;Desvignes et al, 2015;Dosch, 2015). While establishing the relevance of these maternal mRNAs in other teleost species awaits additional studies (e.g.…”

“…Pou2 also regulates epiboly, which occurs during gastrulation and involves spreading and thinning of the three layers specified in the blastula stage. In zebrafish, maternal retinitis pigmentosa 2 (Rp2) protein translated from the maternal rp2 gene is required for establishment of left-right asymmetry (Desvignes et al, 2015). Maternal-effect mutants showing disruption in the functioning of the enveloping cell layer (EVL), in the deep layer (DEL) beneath it, and in the YSL have been identified.…”

Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

“…Maternal genes whose RNA or protein products present in oocytes, fertilized egg or early stage of embryo play an important role in the proper developmental stages [ 1 , 2 ]. In the early stages of development, the transition of material to the zygote is accomplished by two processes: the degradation of maternal products and the initiation of the transcription of the zygotic genome [ 3 – 5 ]. Maternal genes have been well studied in many species, such as humans, mouse, zebrafish and so on [ 3 , 5 – 9 ].…”

“…In the early stages of development, the transition of material to the zygote is accomplished by two processes: the degradation of maternal products and the initiation of the transcription of the zygotic genome [ 3 – 5 ]. Maternal genes have been well studied in many species, such as humans, mouse, zebrafish and so on [ 3 , 5 – 9 ]. In insects, maternal genes and their functions were well known across various Drosophila species [ 10 – 14 ].…”

Genome-wide identification of novel ovarian-predominant miRNAs: new insights from the medaka (Oryzias latipes)

“…During oogenesis, maternal transcripts and proteins are produced and accumulated in oocytes to prepare for meiosis resumption and early embryo development1. Genes that exhibit an oocyte-predominant expression pattern have important functions during oogenesis and early embryogenesis234. These genes are also called oocyte-specific genes2.…”