XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination

Abstract

In Xenopus, an asymmetric distribution of Wnt activity that follows cortical rotation in the fertilized egg leads to the dorsal-ventral (DV) axis establishment. However, how a clear DV polarity develops from the initial difference in Wnt activity still remains elusive. We report here that the Teashirt-class Zn-finger factor XTsh3 plays an essential role in dorsal determination by enhancing canonical Wnt signaling. Knockdown of the XTsh3 function causes ventralization in the Xenopus embryo. Both in vivo and in vitro studies show that XTsh3 substantially enhances Wnt signaling activity in a b-catenin-dependent manner. XTsh3 cooperatively promotes the formation of a secondary axis on the ventral side when combined with weak Wnt activity, whereas XTsh3 alone has little axis-inducing ability. Furthermore, Wnt1 requires XTsh3 for its dorsalizing activity in vivo. Immunostaining and protein analyses indicate that XTsh3 is a nuclear protein that physically associates with b-catenin and efficiently increases the level of b-catenin in the nucleus. We discuss the role of XTsh3 as an essential amplifying factor of canonical Wnt signaling in embryonic dorsal determination.

teashirt is required for head-versus-tail regeneration polarity in planarians

“…The presence of multiple copies of this atypical zinc-finger motif is a hallmark of Teashirt family proteins (Manfroid et al, 2004). Smed-Teashirt lacks the basic motif, the homeodomain and the second C-terminal zinc finger found in vertebrate orthologs, which are also lacking in Drosophila Teashirt and the Drosophila Teashirt paralog Tiptop (Onai et al, 2007). The three mouse teashirt genes can rescue the Drosophila teashirt loss-of-function phenotype, suggesting that Teashirt proteins have similar biochemical activities in highly divergent animals (Manfroid et al, 2004).…”

“…XTsh3 inhibition causes ventralization, a phenotype also seen following perturbation of β-catenin (Onai et al, 2007). XTsh3 can enhance Wnt signaling activity in a β-catenin-dependent manner (Onai et al, 2007). In both flies and frogs, Teashirt can localize to the nucleus and bind β-catenin, but its exact molecular function remains unclear Onai et al, 2007).…”

“…In Xenopus, a Teashirt homolog (XTsh3) is expressed at the presumptive dorsal embryo side near the site of gastrulation. XTsh3 inhibition causes ventralization, a phenotype also seen following perturbation of β-catenin (Onai et al, 2007). XTsh3 can enhance Wnt signaling activity in a β-catenin-dependent manner (Onai et al, 2007).…”

“…XTsh3 can enhance Wnt signaling activity in a β-catenin-dependent manner (Onai et al, 2007). In both flies and frogs, Teashirt can localize to the nucleus and bind β-catenin, but its exact molecular function remains unclear Onai et al, 2007). In other vertebrates, Teashirt proteins have been implicated in myogenesis and in the development of the nervous system, particularly the specification of hindbrain structures; whether Teashirt functions with the Wnt pathway is unknown in several of these contexts (Koebernick et al, 2006;Caubit et al, 2010;Erickson et al, 2011).…”

Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control

“…Tsh-related genes (Tshz) have been characterized in vertebrates (Caubit et al, 2000(Caubit et al, , 2008Manfroid et al, 2004;Koebernick et al, 2006;Coré et al, 2007;Onai et al, 2007;Kajiwara et al, 2009;Jenkins et al, 2010); however, their role in the development of the mammalian CNS is poorly understood. We previously reported that teashirt 3 (Tshz3) mutant mice develop to term but fail to breathe and die quickly at birth (Caubit et al, 2008), suggesting that Tshz3 might play a role in the development of the peripheral and/or central control of respiration.…”