Zebrafish Dpr2 Inhibits Mesoderm Induction by Promoting Degradation of Nodal Receptors

Abstract

Nodal proteins, members of the transforming growth factor-beta (TGFbeta) superfamily, have been identified as key endogenous mesoderm inducers in vertebrates. Precise control of Nodal signaling is essential for normal development of embryos. Here, we report that zebrafish dapper2 (dpr2) is expressed in mesoderm precursors during early embryogenesis and is positively regulated by Nodal signals. In vivo functional studies in zebrafish suggest that Dpr2 suppresses mesoderm induction activities of Nodal signaling. Dpr2 is localized in late endosomes, binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors.

Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2

“…Although I found that ␤-catenin, Sqt, and Boz could induce ectopic dpr1 and dpr2 expression, only ␤-catenin signaling was required for their initiation. In contrast to what has been reported by Zhang et al (2004), Nodal signaling was only required for maintenance of mesodermal dpr1 and dpr2 expression in the margin during gastrulation. I also found that inhibition of the ventralizing signal bone morphogenetic protein (BMP) by the BMP-antagonist Noggin led to ectopic expression of dpr1 and dpr2.…”

“…Both dpr1 and dpr2 are expressed on the prospective dorsal side of the embryo shortly after the initiation of zygotic transcription (Zhang, 2004;Waxman et al, 2004). In contrast to what is observed in Xenopus, we have found that Dpr1 is not required for organizer formation but rather aids Wnt8 promotion of ventroposterior patterning (Waxman et al, 2004).…”

“…Dpr2 is required for morphogenetic movements during gastrulation (Waxman et al, 2004). In addition, a recent study by Zhang et al (2004) implicates Dpr2 in Nodal signaling.…”

“…We and others have characterized expression of zebrafish dpr1/frd1 and dpr2/frd2, here referred to as dpr1 and dpr2 (Gillhouse et al, 2004;Zhang, 2004;Waxman et al, 2004). Both dpr1 and dpr2 are expressed on the prospective dorsal side of the embryo shortly after the initiation of zygotic transcription (Zhang, 2004;Waxman et al, 2004).…”

“…Because both dpr1 and dpr2 are expressed on the prospective dorsal side of the zebrafish embryo shortly after the midblastula transition (Zhang et al, 2004;Waxman et al, 2005), I postulated that they might be targets of ␤-catenin or downstream gastrula organizer genes. Although I found that ␤-catenin, Sqt, and Boz could induce ectopic dpr1 and dpr2 expression, only ␤-catenin signaling was required for their initiation.…”