Eaf1 and Eaf2 mediate zebrafish dorsal-ventral axis patterning via suppressing Wnt/β-Catenin activity

Abstract

During early vertebrate embryogenesis, maternal Wnt/β-catenin signaling is thought to locally initiate expression of dorsal-specific genes. Here, eaf1 and eaf2 were identified as important maternal and zygotic modulators of Wnt signaling to initiate and specify ventral genes. Expression of ventral ved, vent, and vox was all obviously enhanced in either maternal or zygotic eaf1/2 morphants, and in both eaf1 heterozygous and homozygous mutants, but their expression was suppressed in embryos with over-expression of eaf1/2. Additionally, eaf1/2 were revealed to suppress ventral fates in embryos via Wnt/β-catenin1/Tcf signaling, complimentary to their roles in suppressing dorsal fates via Wnt/β-catenin2 signaling. Moreover, eaf1/2 were also revealed to obviously suppress the expression of axin2 induced by β-catenin2 rather than by β-catenin1, and the dorsal expression of axin2 in embryos was obviously suppressed by ectopic expression of eaf1/2. This study uncovers a novel dorsal-ventral patterning pathway, with eaf1 and eaf2 inhibiting ventral cells via suppressing Wnt/β-catenin1/Tcf signaling and inducing dorsal cells indirectly via suppressing β-catenin2-induced-axin2 on the dorsal side of embryos.

Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance

“…The eaf1- deleted zebrafish has been constructed in our lab and reported recently (Fig. S 1 A1) (Liu et al 2017 ; Liu et al 2018 ), and eaf2- deleted zebrafish was constructed in this study (Fig. S 1 A2).…”

“…Eaf1/2 were unveiled to regulate the anterior-posterior pattern of zebrafish axis by modulating WNT/β-catenin signaling (Liu et al 2018 ; Liu et al 2013 ), which was shown to be involved in the hematopoietic developmental processes, such as early hematopoiesis and erythroid specification (Tarafdar et al 2013 ; Wilusz and Majka 2008 ). In this study, we used WISH to examine the expression of Wnt signaling ligands wnt3 and wnt16 , WNT-activated receptor ( fzd2 ), and axin2 (a target of WNT/β-catenin signaling) in eaf1 −/− and eaf2 −/− embryos or larvae at 16 hpf, 24 hpf, or 72 hpf, respectively.…”

“…Several studies have revealed the functions and molecular characteristics of EAF1/2 in Arabidopsis (Dabas et al 2021 ; Scott et al 1999 ), Saccharomyces cerevisiae (Laframboise and Baetz 2021 ; Sweta et al 2021 ), Caenorhabditis (Cai et al 2011 ) and mammalian cells (Kenner 2014 ), such as in cell growth (Dabas et al 2018 ), cell immortalization (Dimartino et al 2000 ) and in melanoma and leukemogenesis (Luo et al 2001 ; Polak et al 2003 ). It has been reported that EAF1/2 can act as transcriptional suppressors to inhibit the TGF-β signaling pathway and WNT/β-catenin signaling in the formation of the three germ layers and the anterior and posterior pattern during early zebrafish embryogenesis (Liu et al 2009 ; Liu et al 2017 ; Liu et al 2018 ; Liu et al 2013 ). The level of p-β-Catenin indicates the undegenerated β-Catenin protein and WNT/β-catenin activities (Ahmadzadeh et al 2016 ).…”

“…The purpose of this study was to investigate the effects of EAF1/2 deficiency and the related molecular mechanism on erythropoiesis and hypoxia tolerance in zebrafish. Eaf1 −/− mutant with 5 bp deletion in exon1 has been successfully constructed in our laboratory (Liu et al 2018 ). Here, we knocked out eaf2 in zebrafish to generate homozygous mutants and tested the stress resistance of eaf1 −/− and eaf2 −/− mutants to hypoxia infection.…”

Conditional Deletion of Eaf1 Induces Murine Prostatic Intraepithelial Neoplasia in Mice

“…Deletion of eaf-1 in C. elegans resulted in decreased fertility, decreased survival and altered cuticle collagen function [6]. In zebrafish, eaf1 and eaf2 appear to have overlapping function in modulating Wnt signaling during embryonic development [7].…”