In amphibians, the sperm entry and subsequent cortical rotation determines the side that will become dorsal. A high ß-catenin concentration arises at a position displaced from the vegetal pole. This forms the so-called Nieuwkoop center within the endoderm. It is assumed that this center triggers the proper Spemann Organizer. This raises two questions: (i) Why is organizer formation a two-step process? (ii) How is a second eccentric organizing region generated in systems without pre-localized determinants?
After the generation of the mesoderm as described above, it could appear as a straightforward mechanism to generate a new hot spot, the Spemann Organizer, within the mesoderm. Corresponding simulations pointed to an unexpected problem that may provide an answer. Since the diameter of the marginal zone is large, an inhibitor produced in the incipient organizing region would dilute excessively by spreading into the whole blastula and become incapable of repressing the formation of a second organizer at the opposite side of the mesodermal ring:
The intermediate formation of a signaling center displaced from the poles provides a solution: If an organizing region is generated close to but displaced from a pole, only a smaller region is involved in the pattern-forming reaction. This allows for rapid and efficient patterning and ensures that only one hot spot survives. Moreover, the pattern-forming process can occur at a much earlier stage, before mesoderm is formed and before cleavage has led to many cells that may hamper the exchange of molecules. The strong asymmetry provided by the signals from the center ensures that in further patterning events the most dorsal position is clearly distinguished. Thus, the formation of an early eccentric organizing region (e. g., the Nieuwkoop center) may be the crucial pattern forming step ascertaining that only a single dorsal organizer emerges at later stages. The formation of a second hot spot in this manner can be accomplished if the first organizer activates the second at long-range, but inhibits it locally:
The situation should be clarified by an analogy: After assigning the north and south pole of a globe, the equatorial zone and a hot spot thereupon can be defined. This, however, would require a competition along the whole equatorial zone if only a single spot on the equator should be allowed. Since an inhibitor would be also diluted into non-equatorial regions, the formation of a second spot at the opposite position is hardly avoidable. To solve this problem it is proposed that shortly after the definition of the south pole, a second special region is generated that is eccentric to the south pole (like New Zeeland). In this way the symmetry is broken. This can be done at a much earlier stage, before the formation of the equatorial zone is finished. The asymmetry generated in this way restrict the possible region at which later the equatorial spot can emerge.
Involved in the generation of this eccentric Nieuwkoop center are molecules such as WNT, ß-catenin, Tcf3 and siamois. As mentioned, Nieuwkoop  observed that the notochord and the neural tube could also form in aggregates, i.e., after waiving out the asymmetric localization of determinants. Together with the function of the Nieuwkoop center discussed above, this suggests that the ß-catenin – siamois pathway is not only involved in bringing pre-localized determinants to function but is also part of a real pattern forming system. This is supported by the experimental findings that siamois has a feedback on its own activation  and that an ectopic activation can cause a complete secondary axis . As further confirmation of the model, it would be very interesting to learn whether siamois activation or other elements of the WNT pathway also become locally active in Nieuwkoop aggregates. It is remarkable that least the first three molecules are also involved in the head signaling of hydra. Thus, the formation of primary organizing regions is seems to be under control of universally used molecules.