The roles of three signaling pathways in the formation and function of the Spemann Organizer

Abstract

Since the three main pathways (the Wnt, VegT and BMP pathways) involved in organizer and axis formation in the Xenopus embryo are now characterized, the challenge is to understand their interactions. Here three comparisons were made. Firstly, we made a systematic comparison of the expression of zygotic genes in sibling wild-type, VegT-depleted (VegT–), β-catenin-depleted (β-catenin–) and double depleted (VegT–/β-catenin–) embryos and placed early zygotic genes into specific groups. In the first group some organizer genes, including chordin, noggin and cerberus, required the activity of both the Wnt pathway and the VegT pathway to be expressed. A second group including Xnr1, 2, 4 and Xlim1 were initiated by the VegT pathway but their dorsoventral pattern and amount of their expression was regulated by the Wnt pathway. Secondly, we compared the roles of the Wnt and VegT pathways in producing dorsal signals. Explant co-culture experiments showed that the Wnt pathway did not cause the release of a dorsal signal from the vegetal mass independent from the VegT pathway. Finally we compared the extent to which inhibiting Smad 1 phosphorylation in one area of VegT–, or β-catenin– embryos would rescue organizer and axis formation. We found that BMP inhibition with cm-BMP7 mRNA had no rescuing effects on VegT– embryos, while cm-BMP7 and noggin mRNA caused a complete rescue of the trunk, but not of the anterior pattern in β-catenin– embryos.

Maternal Factors and Nodal Autoregulation Orchestrate Nodal Gene Expression for Embryonic Mesendoderm Induction in the Zebrafish

“…As essential mesendoderm inducers, the expression of zygotic nodal genes is activated by maternal factors soon after midblastula transition (MBT), which happens in zebrafish embryos around 3 h postfertilization (hpf) (1 k-cell stage) ( Kimmel et al, 1995 ). In frog blastulas, the maternal T-box transcription factor VegT activates the expression of Xenopus Nodal-related ( Xnr ) genes in the vegetal blastomeres and maternally regulated nuclear β-catenin in dorsal blastomeres acts in synergy with VegT to enhance Xnr genes expression so that a Nodal gradient is formed along the dorsal-ventral axis to induce and pattern the mesendoderm ( Zhang et al, 1998 ; Kofron et al, 1999 ; Agius et al, 2000 ; Takahashi et al, 2000 ; Rex et al, 2002 ; Xanthos et al, 2002 ). In the zebrafish, ndr1 and ndr2 genes are initially activated in the dorsal blastodermal margin at about 3.3 h hpf and 3.7 hpf respectively, and their expression domains then extend throughout the blastodermal margin to induce the mesendodermal fate ( Feldman et al, 1998 ; Rebagliati et al, 1998 ).…”

The Organizer and Its Signaling in Embryonic Development

“…Third, the three germ layers will respond to the organizer’s signals [ 6 ]. Since the initial research carried out mainly by Spemann and Harland, in recent decades many experiments have been carried out to provide more knowledge about the function of the Spemann–Mangold organizer during embryonic development [ 3 , 5 , 7 , 8 , 9 , 10 ]. It has been found that the amphibious Spemann–Mangold organizer has developmental analogues in other vertebrates [ 11 ].…”

Characterization of convergent thickening, a major convergence force producing morphogenic movement in amphibians

“…The onset of CT at Stage 10- appears linked to the activation of the basal mesodermal program by maternal VegT and subsequent Nodal signaling, via phospho-Smad2 ( Kofron et al, 1999 ; Kavka and Green, 2000 ; Lee et al, 2001 ; Xanthos et al, 2002 ), since it does not occur in embryos treated with the small molecule inhibitor sb-505124 (Shook, personal observation) and the inhibition of Nodal expression by pharmacological or genetic means blocks both blastopore formation and all subsequent gastrulation movements ( Horb and Thomsen, 1997 ; Kofron et al, 1999 ; Luxardi et al, 2010 ). CT is independent of Spemann’s Organizer and the downstream dorsal patterning pathways responsible for turning on CE, since it still occurs in ventralized embryos.…”