Advantages of the Xenopus model system
External development and large numbers of embryos make studies of the earliest stages of development very accessible.
Good tools to modulate gene expression are available, such as mRNA injection and antisense technology. We are using these tools extensively to study aspects of the earliest embryonic gene regulation.
Biochemistry of early development is possible in this system, including protein complex purification and the analysis of chromatin structure and promoter nucleo-protein architecture. The availability of large numbers of oocytes and externally developing embryos makes biochemistry feasible and existing Xenopus in vitro systems (G. Almouzni and A.P. Wolffe, 1993) very powerful.
Experimental embryology using transplantation approaches and the animal cap system (inducible embryonic cells) in Xenopus has laid the foundation of our current knowledge of early embryonic inductions and the cellular and molecular basis of development. Inductive signals can be studied in the animal cap system. For example, animal caps incubated with Activin or FGFs induce neurectoderm through the induction of mesoderm, whereas dilution of BMP signaling by cell dissociation induces neurectoderm directly. Neural induction in this system can be modified in order to induce specific types of neurectoderm, specifying for example an anterior or posterior identity (C.Kiecker and C.Niehrs, 2001; M.Taira et al., 1997).
Inducible embryonic cells from Xenopus embryos (animal caps) are ideally suited to study the physiological roles of DNA methylation and methyl CpG binding proteins in embryonic differentiation, as the animal caps are derived directly from early embryos. In contrast, cells kept in culture for many passages undergo changes in genomic DNA methylation due to Darwinian growth selection pressures (S.Goldstein et al., 1985; P.A.Jones et al., 1990; F.Antequera et al., 1990).
Studies of early embryonic gene function in the Xenopus system have contributed enormously to elucidating the molecular properties and functional roles of mammalian genes, including genes involved in human disease (see for examples: L.B.Zimmerman et al., 1996; Y.Gong et al., 1999; M.Molenaar et al., 1996; V.Korinek et al., 1997; D.Wang et al., 2001).
Experiments performed with Xenopus have served to provide powerful paradigms in molecular, cellular, developmental and cancer biology. It is a very good model system for exploring molecular mechanisms of gene regulation and for studying the earliest stages of vertebrate embryonic development.