Important advances have been made in our understanding of the events that pattern the early Xenopus embryo. We appreciate the central importance of maternal regulators in this process and recognize the crucial roles of antagonists, such as transcriptional and cell cycle repressors, and a surprising number of signaling inhibitors. We are perceptibly nearer to understanding the essential roles of the four signaling pathways in ectoderm, mesoderm and endoderm specification (Fig. 8), and the mechanism of gastrulation. Nevertheless, early development continues to surprise. Outstanding mysteries include: the mechanism by which VegT mRNA carries out an architectural role in mRNA localization during oogenesis; the control of vegetal rotation movements in the endoderm; and how Wnt11 can have both canonical and non-canonical roles. And what would be the state of determination of gastrula cells in which BMP, Xnr, Wnt and FGF signaling was prevented?
The next phase of investigation involves an embarrassment of riches. The Xenopus Genome Initiative and array technology mean that we will all have long lists of target genes to study. Mutagenesis studies in Xenopus tropicalis (Grammer et al., 2005) and easy transgenesis methods (Pan et al., 2006) will provide us with a new wave of phenotypes to analyze. Some reassurance that it will be possible to place the new knowledge of gene function into correct regulatory networks comes from the fact that we can validate our findings by rescue experiments. Furthermore, basic principles are emerging that show a similarity of process among all the germ layers. Examples include the regulation of AP patterning by Hox genes, repression of cell division preceding cell movement and differentiation, and the recurring theme of global transcriptional repression and localized activation. And, if we finally master gastrulation, the next challenge will be organogenesis.
I am extremely grateful to Stephanie Lang for help with references, and to Chris Wylie, Bilge Birsoy, Jane Alfred and anonymous reviewers for critically reading the work. Work in my laboratory is supported by the NIH RO1 HD33002 and HD38272.