The prevailing model of dorsal ventral patterning of the amphibian embryo predicts that the prospective mesoderm is regionalized at gastrulation in response to a gradient of signals. This gradient is established by diffusible BMP and Wnt

The concept of the Spemann organizer has dominated our understanding of early vertebrate development. In amphibians, the organizer corresponds to a small dorsal sector of the gastrula marginal zone (~60°); if experimentally transplanted to the ventral region, these cells induce a complete ectopic axis in the recipient tissue (Spemann and Mangold, 1924). In molecular terms, the organizer functions by secreting diffusible inhibitors of the Wnt and BMP pathways (De Robertis et al., 2001; Harland and Gerhart, 1997). Therefore, in a model similar to the original gradient proposal of Wolpert (Wolpert, 1989), the marginal zone of the gastrula would manifest extreme dorsal cell fates at low levels of BMPs and Wnts, and extreme ventral cell fates at high levels of these signaling molecules. Intermediate fates may be elicited by intermediate levels. Although the dominance of the dorsal signals is obvious (transplanting ventral cells to the dorsal side does not produce an ectopic ventral axis), it does not follow that all of the remaining tissue merely responds to levels of signals dictated by the organizer. It is possible that patterning in the ventral and lateral domains is only weakly dependent on the dorsal signals, although still subservient to them. The ventral region may rely on self-organizing processes to regulate behavior and fate of the cells at a distance from the organizer. When Wnt and BMP inhibitors diffusing from the dorsal side fall below a certain threshold, these ventral organizing activities would be activated and much of the pattern would be generated by them, rather than by the concentration of the inhibitors. Most phenomenological experiments, such as those of Spemann and Mangold do not distinguish between these possibilities. There is much complexity to control on the ventral side, including the allocation of cells to the lateral plate mesoderm, muscle, pronephros and blood (Davidson and Zon, 2000; Hemmati-Brivanlou and Thomsen, 1995), and there is some evidence for processes of ventral organization being more complex than simply reading out a gradient of BMP and Wnt signals created by inhibitors secreted from the organizer (Munoz-Sanjuan and Hemmati-Brivanlou, 2001). For example, not all mesoderm is converted to blood in UV-irradiated embryos. Analogously, in embryos ventralized by dorsal injection of BMP4 or DNxTCF3, it is possible to distinguish a defined domain of globin expression in the absence of the organizer (Kumano and Smith, 2000). The BMP and Wnt pathways themselves interact and are capable of generating considerable complexity (Hoppler and Moon, 1998; Marom et al., 1999). Part of the patterns of ventrolateral mesoderm undoubtedly originates from reciprocal modulation of these two signals (Dale and Jones, 1999; De Robertis et al., 2001). But are different ventrolateral fates determined simply by the distance from the dorsal organizer, or are there self-organizing Development 130, 805-816 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00306