Maternal miR-202-5p is required for zebrafish primordial germ cell migration by protecting small GTPase Cdc42

Abstract

<jats:title>Abstract</jats:title> <jats:p>In many lower animals, germ cell formation, migration, and maintenance depend on maternally provided determinants in germ plasm. In zebrafish, these processes have been extensively studied in terms of RNA-binding proteins and other coding genes. The role of small non-coding RNAs in the regulation of primordial germ cell (PGC) development remains largely unknown and poorly investigated, even though growing interests for the importance of miRNAs involved in a wide variety of biological processes. Here, we reported the role and mechanism of the germ plasm-specific miRNA miR-202-5p in PGC migration: (i) both maternal loss and knockdown of miR-202-5p impaired PGC migration indicated by the mislocalization and reduced number of PGCs; (ii) cdc42se1 was a direct target gene of miR-202-5p, and overexpression of Cdc42se1 in PGCs caused PGC migration defects similar to those observed in loss of miR-202-5p mutants; (iii) Cdc42se1 not only interacted with Cdc42 but also inhibited cdc42 transcription, and overexpression of Cdc42 could rescue PGC migration defects in Cdc42se1 overexpressed embryos. Thus, miR-202-5p regulates PGC migration by directly targeting and repressing Cdc42se1 to protect the expression of Cdc42, which interacts with actin to direct PGC migration.</jats:p>

MiR-202-5p Inhibits RIG-I-Dependent Innate Immune Responses to RGNNV Infection by Targeting TRIM25 to Mediate RIG-I Ubiquitination

“…Many studies have demonstrated that miR-202-5p is an evolutionarily conserved miRNA associating with gonad development in vertebrates [22,27,28]. Recently, we reported that miR-202-5p regulated primordial germ cell migration by directly targeting Cdc42se1 [17]. In this study, we investigated a novel role of miR-202-5p in the immune response to RGNNV infection.…”

“…Zebrafish wild type AB line was purchased from the China zebrafish resource center. MiR-202-5p -/zebrafish were generated in our laboratory previously [17]. Fish were raised at 28 • C with 10 h darkness and 14 h light and were fed with commercial pellets twice a day.…”

lncRNA deleted in lymphocytic leukaemia 1 (DLEU1) promotes the migration and invasion of human embryonic trophoblast cells

“…Interestingly, hsa-miR-6511a-5p and hsa-miR-1910-3p all closely interacted with CDC42SE1. Jin and colleagues pointed out that CDC42SE1 not only targeted CDC42, but also suppressed CDC42 expression, and that the miR-202-5p/CDC42SE1 axis could regulate primordial germ cell migration by protecting CDC42 expression of CDC42 (Jin et al, 2019). Additionally, hsa-miR-144-3p was linked with three genes (ROCK1, CDC42EP3 and ARHGAP26).…”

Rho GTPases Signaling in Zebrafish Development and Disease

“…Moreover, Cdc42 and RhoL are known to control normal transfer of cytoplasm from nurse cells to oocyte in Drosophila [61] and Cdc42 knockdown in C elegans induces disruption of gonad primordium as well as absence of primordial germ cells [62]. As highlighted for Rac1, zebrafish Cdc42 can also impact the behavior of the highly migratory germ cells through its ability to control Blebs' expansion in migrating germ cells in vivo [63]. This is also relevant for other cell types such as mesendodermal cells [64], however, this is not the case in NC cells, since Syndecan 4 signaling pathway relies on Rac1 activity but not Cdc42 [18].…”