Wnt proteins are now recognized as one of the major families of developmentally important signaling molecules, with mutations in Wnt genes displaying remarkable phenotypes in the mouse, Caenorhabditis elegans, and Drosophila. Among functions provided by Wnt proteins are such intriguing processes as embryonic induction, the generation of cell polarity, and the specification of cell fate. Until recently, our knowledge of the molecular mechanism of Wnt signaling was very limited, but over the past year, several major gaps have been filled. These include the identification of cell-surface receptors and a novel mechanism of relaying the signal to the cell nucleus. In addition, several components of Wnt signaling are implicated in the genesis of human cancer. These insights have come from different corners of the animal kingdom and have converged on a common pathway. At this junction in this rapidly evolving field, we review our current understanding of Wnt function and signaling mechanisms, doing so in a comparative approach. We have put emphasis on the latest findings, highlighting novelty and underscoring questions that remain. For additional literature, we refer to several previous reviews (McMahon 1992; Nusse and Varmus 1992; Klingensmith and Nusse 1994; Miller and Moon 1996; Moon et al. 1997). We have limited the number of references, particularly in the tables. Fully referenced forms of these tables can be found on the Wnt homepage (http://wwwleland.stanford.edu/∼rnusse/wntwindow.html).

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Wnt signaling: a common theme in animal development

Wnt genes encode a large family of secreted, cysteine-rich proteins that play key roles as intercellular signaling molecules in development. Genetic studies in Drosophila and Caenorhabditis elegans, ectopic gene expression in Xenopus, and gene knockouts in the mouse have demonstrated the involvement of Wnts in processes as diverse as segmentation, CNS patterning, and control of asymmetric cell divisions. The transduction of Wnt signals between cells proceeds in a complex series of events including post-translational modification and secretion of Wnts, binding to transmembrane receptors, activation of cytoplasmic effectors, and, finally, transcriptional regulation of target genes. Over the past two years our understanding of Wnt signaling has been substantially improved by the identification of Frizzled proteins as cell surface receptors for Wnts and by the finding that beta-catenin, a component downstream of the receptor, can translocate to the nucleus and function as a transcriptional activator. Here we review recent data that have started to unravel the mechanisms of Wnt signaling.

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Mechanisms of wnt signaling in development

Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration.

https://science.sciencemag.org/content/sci/298/5601/2188.full.pdf

Heart Regeneration in Zebrafish

The Wnt signalling pathway is an ancient system that has been highly conserved during evolution. It has a crucial role in the embryonic development of all animal species, in the regeneration of tissues in adult organisms and in many other processes. Mutations or deregulated expression of components of the Wnt pathway can induce disease, most importantly cancer. The first gene to be identified that encodes a Wnt signalling component, Int1 (integration 1), was molecularly characterized from mouse tumour cells 25 years ago. In parallel, the homologous gene Wingless in Drosophila melanogaster, which produces developmental defects in embryos, was characterized. Since then, further components of the Wnt pathway have been identified and their epistatic relationships have been defined. This article is a Timeline of crucial discoveries about the components and functions of this essential pathway.

Wnt signalling and its impact on development and cancer

A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in vivo imaging at 1.5 billion voxels per minute provides “digital embryos,” that is, comprehensive databases of cell positions, divisions, and migratory tracks. Our analysis of global cell division patterns reveals a maternally defined initial morphodynamic symmetry break, which identifies the embryonic body axis. We further derive a model of germ layer formation and show that the mesendoderm forms from one-third of the embryo's cells in a single event. Our digital embryos, with 55 million nucleus entries, are provided as a resource.

/pdf/reconstruction-of-zebrafish-early-embryonic-development-by-4drm9luiek.pdf

Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy.

β-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos

An enzyme present in extracts from calf thymus degrades specifically the RNA moiety of DNA-RNA hybrids. Other nucleic acids, such as single- or double-stranded DNA and single- or double-stranded RNA, are not affected to a comparable degree. If prepared free of the hybrid-degrading enzyme, RNA polymerase from calf thymus shows a fivefold increase in activity on denatured DNA as compared to native DNA.

https://science.sciencemag.org/content/sci/166/3903/393.full.pdf

Enzyme from Calf Thymus Degrading the RNA Moiety of DNA-RNA Hybrids: Effect on DNA-Dependent RNA Polymerase

Changes in the nuclear lamina composition during early development of Xenopus laevis.

Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids.

Xenopus laevis is the key model for developmental, differential and embryological studies in vertebrates. Using molecular biological techniques it has become possible within the last few years to analyze developmental processes up to the level of genes. On obtaining results it is necessary to correlate them with morphological and histological stages. This excellent work documents and describes such developmental stages in finite detail. After an informative introduction to The Early Development of Xenopus laevis follows the highlight of the book, namely the 42 plates, each consisting of at least four high resolution micrographs. The reader is thus provided with a histological presentation of immaculate quality. Each plate is complemented by a schematic diagram describing the details shown on the plate, an additional scheme indicating the section and an explanatory short text, making this a potentially highly sought after work.

Peter Hausen

Papers

β-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos

Enzyme from Calf Thymus Degrading the RNA Moiety of DNA-RNA Hybrids: Effect on DNA-Dependent RNA Polymerase

Changes in the nuclear lamina composition during early development of Xenopus laevis.

Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids.

The Early Development of Xenopus Laevis: An Atlas of the Histology