NORMAL GENOMIC

• Hikasa H, Shibata M, Hiratani I, Taira M
• The Xenopus receptor tyrosine kinase Xror2 modulates morphogeneticmovements of the axial mesoderm and neuroectoderm via Wnt signaling.
• Development. 2002; 129: 5227-39
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• The Spemann organizer plays a central role in neural induction, patterningof the neuroectoderm and mesoderm, and morphogenetic movements duringearly embryogenesis. By seeking genes whose expression is activated by theorganizer-specific LIM homeobox gene Xlim-1 in Xenopus animal caps, weisolated the receptor tyrosine kinase Xror2. Xror2 is expressed initiallyin the dorsal marginal zone, then in the notochord and the neuroectodermposterior to the midbrain-hindbrain boundary. mRNA injection experimentsrevealed that overexpression of Xror2 inhibits convergent extension of thedorsal mesoderm and neuroectoderm in whole embryos, as well as theelongation of animal caps treated with activin, whereas it does not appearto affect cell differentiation of neural tissue and notochord.Interestingly, mutant constructs in which the kinase domain waspoint-mutated or deleted (named Xror2-TM) also inhibited convergentextension, and did not counteract the wild-type, suggesting that theectodomain of Xror2 per se has activities that may be modulated by theintracellular domain. In relation to Wnt signaling for planar cellpolarity, we observed: (1) the Frizzled-like domain in the ectodomain isrequired for the activity of wild-type Xror2 and Xror2-TM; (2)co-expression of Xror2 with Xwnt11, Xfz7, or both, synergisticallyinhibits convergent extension in embryos; (3) inhibition of elongation byXror2 in activin-treated animal caps is reversed by co-expression of adominant negative form of Cdc42 that has been suggested to mediate theplanar cell polarity pathway of Wnt; and (4) the ectodomain of Xror2interacts with Xwnts in co-immunoprecipitation experiments. These resultssuggest that Xror2 cooperates with Wnts to regulate convergent extensionof the axial mesoderm and neuroectoderm by modulating the planar cellpolarity pathway of Wnt.

• Nieto MA
• Reorganizing the organizer 75 years on.
• Cell. 1999; 98: 417-25

• Gumbiner BM
• Propagation and localization of Wnt signaling.
• Curr Opin Genet Dev. 1998; 8: 430-5
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• Cellular mechanisms for the transport and localization of Wnt signalingcomponents are important for the propagation, distribution, andpolarization of Wnt signals in embryonic tissues. Wnt signals aredistributed through tissues by vesicular transport of Wnt proteins,localized in embryos by directed transport of cytoplasmic Wnt-signalingcomponents, and propagated asymmetrically during cell division.

• Carnac G, Kodjabachian L, Gurdon JB, Lemaire P
• The homeobox gene Siamois is a target of the Wnt dorsalisation pathway andtriggers organiser activity in the absence of mesoderm.
• Development. 1996; 122: 3055-65
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• Siamois, a Xenopus zygotic homeobox gene with strong dorsalising activity,is expressed in the dorsal-vegetal organiser known as the Nieuwkoopcentre. We show that, in contrast to Spemann organiser genes such asgoosecoid, chordin and noggin, Siamois gene expression is not inducedfollowing overexpression of mesoderm inducers in ectodermal (animal cap)cells. However, Siamois is induced by overexpressing a dorsalising Wntmolecule. Furthermore, like Wnt, Siamois can dorsalise ventral mesodermand cooperate with Xbrachyury to generate dorsal mesoderm. These resultssuggest that Siamois is a mediator of the Wnt-signalling pathway and thatthe synergy between the Wnt and mesoderm induction pathways occursdownstream of the early target genes of these two pathways. Overexpressionof Siamois in animal cap cells reveals that this gene can act in a nonvegetal or mesodermal context. We show the following. (1) Animal cap cellsoverexpressing Siamois secrete a factor able to dorsalise ventral gastrulamesoderm in tissue combination experiments. (2) The Spemannorganiser-specific genes goosecoid, Xnr-3 and chordin, but not Xlim.1, areactivated in these caps while the ventralising gene Bmp-4 is repressed.However, the dorsalising activity of Siamois-expressing animal caps issignificantly different from that of noggin- or chordin-expressing animalcaps, suggesting the existence of other dorsalising signals in the embryo.(3) Ectodermal cells overexpressing Siamois secrete a neuralising signaland can differentiate into cement gland and, to a lesser extent, intoneural tissue. Hence, in the absence of mesoderm induction, overexpressionof Siamois is sufficient to confer organiser properties on embryoniccells.

• Dawid IB
• Intercellular signaling and gene regulation during early embryogenesis ofXenopus laevis.
• J Biol Chem. 1994; 269: 6259-62