Dev Genes Evol (2011) 221:255–279 all experimental data, we feel that this or a similar gradient model maybe more adequate to explain the various bic phenotypes. Its main attraction is the ease with which mirror-image duplications of varying size and reversal of polarity are produced by lowering the concentration of a single component’ (Nüsslein-Volhard 1977). After a short postdoc with Klaus Sander in Freiburg, Nüsslein-Volhard took, together with Eric Wieschaus, a junior group leader position at the EMBL in Heidelberg where they conducted their Nobel prize-winning screen for zygotic embryonic lethal mutations (Nüsslein-Volhard and Wieschaus 1980). In the long run, this work would completely change the basis for any theory of pattern formation. For the first time, complete, or almost complete genetic networks for partic- ular patterning problems such as segmentation or neuroblast selection would become available and would provide test cases for modelling approaches. After returning to Tübingen, Nüsslein-Volhard also scientifically returned to the maternal morphogen gradients she had discovered as a postdoc in Gehring’s and Sander’s laboratories. The experience gained with the zygotic whole genome screens made it possible to conduct large-scale screens for maternal-effect mutations. Such screens were performed by Trudi Schupbach and Eric Wieschaus in Princeton (Schupbach and Wieschaus 1989, 1991) and by Ruth Lehmann, Kathryn Anderson, Gerd Jürgens and Nüsslein-Volhard in Tübingen. The analysis of mutant phenotypes together with transplantation experi- ments soon revealed that the AP morphogen gradients in the Drosophila egg emanate from localised determinants at the anterior and posterior egg poles. Later, these were shown to be localised mRNAs. At the level of the early embryo, gradient formation did not require self-organised patterning on which the egg asymmetries would only have a weakly orienting influence. Rather, embryogenesis al- ready started with an amazingly high degree of spatial information present in the egg cell (St Johnston and Nüsslein-Volhard 1992). For a while, the dorsoventral (DV) axis seemed to be different. Apparently, DV axis formation did not require localised components within the egg, and thus appeared to be an example for a self- organised patterning system. However, the exciting obser- vations of ectopic axis formation and axis inversions along the DV axis finally could be explained by local signals emanating from cues in the eggshell (Anderson et al. 1985; Stein et al. 1991; Roth 1993). The transition from eggshell cues, though, to the embryonic DV pattern occurs in a dynamic way which apparently has some self-organising properties (Meinhardt 2004; Moussian and Roth 2005; Roth and Schupbach 1994). However, the eggshell cues themselves provide fairly accurate information which can be traced back to a mRNA localised within the developing oocyte (Neuman-Silberberg and Schupbach 1993). Thus, for those instances where we had expected that the theory 267 would be most helpful, a completely different picture had emerged. As Waddington had already indicated in his response to Turing’s paper, intracellular patterning was much more important than anticipated. It became necessary to study how the egg was constructed during oogenesis in order to understand axis formation. One might object that Drosophila and insects in general are unusual because they produce eggs that display bilateral symmetry presaging the two body axes before fertilisation. However, it seems that the lesson learned from Drosophila reflects a more general problem of the early theories of pattern formation. These theories systematically underestimated the potential and importance of intracellular patterning to provide spatial information for the multicellular level or to influence and constrain mechanisms of multicellular patterning. The description of intracellular patterning requires, however, at least in part, approaches different from the mechanisms employed in the original Gierer–Meinhardt model. Since every eukaryotic cell already represents a highly structured three-dimensional object, the spatial information contained in the cell can be used to initiate symmetry-breaking events. Thus, in Drosophila, DV asymmetry arises through asym- metric movement of the oocyte nucleus (Roth and Lynch 2009) or in amphibians, bilateral symmetry depends on rotation of the oocyte cell cortex with regard to the rest of the cell (Larabell et al. 1996; Marrari et al. 2004). These phenomena and other aspects of cell polarisation require dynamic changes of cytoskeletal elements. At this level, theory again becomes relevant. A deeper understanding of cytoskeletal dynamics requires biophysical modelling approaches (Howard 2001). The same applies for other aspects of intracellular patterning which increasingly become subject of mathematical modelling (Karsenti 2008). Meinhardt himself has contributed to some of this work addressing dynamic aspects of cell division in bacteria (Hale et al. 2001; Meinhardt and de Boer 2001) and of the chemotactic behaviour of eukaryotic cells (Meinhardt 1999, 2000). Modern theories of biological pattern formation While the inadequate representation of intracellular pattern- ing addresses the reference level of the theory, the more general problem of early pattern formation theories was the lack of molecular detail. Since none of the developmental processes which the theories described was understood at the molecular level, the theories could not work with realistic molecular assumptions. Activators and inhibitors remained abstract entities. As pointed out, this did not prevent the early theoreticians from gaining major insights which were validated by later research. However, these insights addressed a more generic level representing both