Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus

Abstract

Wnt11 is a secreted protein that signals through the non-canonical planar cell polarity pathway and is a potent modulator of cell behavior and movement. In human, mouse, and chicken, there is a single Wnt11 gene, but in zebrafish and Xenopus, there are two genes related to Wnt11. The originally characterized Xenopus Wnt11 gene is expressed during early embryonic development and has a critical role in regulation of gastrulation movements. We have identified a second Xenopus Wnt11-Related gene (Wnt11-R) that is expressed after gastrulation. Sequence comparison suggests that Xenopus Wnt11-R, not Wnt11, is the ortholog of mammalian and chicken Wnt11. Xenopus Wnt11-R is expressed in neural tissue, dorsal mesenchyme derived from the dermatome region of the somites, the brachial arches, and the muscle layer of the heart, similar to the expression patterns reported for mouse and chicken Wnt11. Xenopus Wnt11-R exhibits biological properties similar to those previously described for Xenopus Wnt11, in particular the ability to activate Jun-N-terminal kinase (JNK) and to induce myocardial marker expression in ventral marginal zone (VMZ) explants. Morpholino inhibition experiments demonstrate, however, that Wnt11-R is not required for cardiac differentiation, but functions in regulation of cardiac morphogenesis. Embryos with reduced Wnt11-R activity exhibit aberrant cell-cell contacts within the myocardial wall and defects in fusion of the nascent heart tube.

Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling

“…The AP1:luciferase reporter activity was also reduced in the Wnt11-depleted endoderm (Supplemental Fig. S8), suggesting that endogenous JNK activity is regulated by Wnt11, consistent with previous reports (Pandur et al 2002;Garriock et al 2005). Later in development, the liver and heart were bifurcated ( Fig.…”

“…6B). While there is no single transduction component that is universally used by all the noncanonical pathways, JNK activation has been implicated (in at least some contexts) in each of the Wnt/ PCP, Wnt/Ca 2+ , and Wnt/Ror2 branches (Pandur et al 2002;Yamanaka et al 2002;Garriock et al 2005;Schambony and Wedlich 2007). One of the downstream targets of JNK is c-jun, which when phosphorylated is a component of the AP1 the transcription factor complex, and thus JNK activity can be measured using an AP1: luciferase transcriptional reporter (Cheyette et al 2002;Park and Moon 2002).…”

“…6D,E), suggesting that Wnt11 and Wnt5 can signal via both the canonical and noncanonical pathways in the foregut. This was surprising because although Wnt11 and Wnt5 have been shown to stimulate either canonical or noncanonical signaling depending on the cellular context (Heisenberg et al 2000;Tada and Smith 2000;Pandur et al 2002;Garriock et al 2005;Tao et al 2005), it was previously unclear whether they could stimulate both pathways in the same cells. Indeed, the canonical and noncanonical Wnt pathways are thought to inhibit one another Topol et al 2003;Mikels and Nusse 2006;Caneparo et al 2007).…”

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

“…The assertion about the timing of the requirement of GATA5 during cardiogenesis is also supported by the fact that we observe some tissue disintegration in 5spMO-injected explants at later stages (data not shown). This observation could be interpreted either as a non-specific offtarget effect of the 5spMO or that GATA5 is required for the cell adhesion process that has been described during heart morphogenesis (Garriock et al, 2005). Although the molecular mechanisms that underlie this phenomenon are currently unclear to us, we believe that this cannot be linked to a non- Fig.…”

“…It also suggests that no other potential non-canonical Wnt signaling ligand, such as Wnt11r (Garriock et al, 2005) mediates the different requirement for GATA5. In support of this assertion, experimental activation of non-canonical Wnt signaling during organogenesis, when Wnt11r is supposed to be active in cardiogenesis (Garriock et al, 2005), is still unable to rescue the effect of GATA5 depletion ( Fig. 8D and E).…”