RNF152 negatively regulates Wnt/β-catenin signaling in Xenopus embryos

Abstract

The Wnt/β-catenin signaling plays crucial roles in early development, tissue homeostasis, stem cells, and cancers. Here, we show that RNF152, an E3 ligase localized to lysosomes, acts as a negative regulator of the Wnt/β-catenin pathway during Xenopus early embryogenesis. Overexpression of wild-type (WT) RNF152 inhibited XWnt8-induced stabilization of β-catenin, ectopic expression of target genes, and activity of a Wnt-responsive promoter. Likewise, an E3 ligase-defective RNF152 had repressive effects on the Wnt-dependent gene responses but not its truncation mutant lacking the transmembrane domain. Conversely, knockdown of RNF152 further enhanced the transcriptional responses induced by XWnt8. RNF152 morphants exhibited defects in craniofacial structures and pigmentation. In line with this, the gain-of-RNF152 function interfered with the expression of neural crest (NC) markers, whereas its depletion up-regulated NC formation in the early embryo. Mechanistically, RNF152 inhibits the polymerization of Dishevelled, which is key to Wnt signaling, in an E3 ligase-independent manner. Together, these results suggest that RNF152 controls negatively Wnt/β-catenin signaling to fine-tune its activity for NC formation in Xenopus embryo.

Phylogenomic analysis of the Lake Kronotskoe species flock of Dolly Varden charr reveals genetic and developmental signatures of sympatric radiation

“…2D )(35). Another included multiple genes of interest including, zswim 5, which is expressed in cranial neural crest cells (36), rnf152 , which is involved in regulating neural crest formation (37), and mc4r , which is a crucial regulator of appetite and metabolism via leptin and thyroid signaling modulation ( Fig. 2E )(38).…”

“…One locus potentially associating with craniofacial differentiation spanned an interval centered on zyg11b which has been implicated in craniofacial microsomia ( Figure 2E )(Tingaud-Sequeira, Trimouille et al 2020). Another locus included multiple genes of interest including, including zswim 5, which is expressed in cranial neural crest (Wong, Rebbert et al 2016), rnf152 , which is involved in regulating neural crest formation (Yoon, Kim et al 2022), and mc4r , which is a crucial regulator of appetite and metabolism via leptin and thyroid signaling modulation ( Figure 2F )(Decherf, Seugnet et al 2010). This suite of craniofacial and metabolic genes may have functioned like a superlocus which was spread via shared introgression between the Bigmouth and Nosed lineages and subsequently reinforced the differentiation of distinct lineages.…”