The Organizer and Beyond

Rehovot 76100 ganizer, positioned on the future dorsal side of the em-Israel bryo, can be viewed as an array of distinct secreted inhibitors that pattern the embryo by antagonizing the activity of ventralizing factors (BMPs and Wnts). Studies In 1924 Hans Spemann and Hilde Mangold carried out in Xenopus have uncovered an amazing diversity of in-an experiment that revolutionized the field of develop-hibitors, dedicated to the BMP pathway (Chordin, Nog-mental biology and biology at large. They transplanted gin, Follistatin), the Wnt pathway (Frzb, Dickkopf, and tissue from the dorsal blastopore lip of a developing Crescent), or both (Cerberus) (De Robertis et al., 2000). Xenopus embryo into the future ventral region of another In view of the evolutionary conservation of the major embryo. The result was the development of a precise signaling pathways, it is striking that many of the inhibi-duplication of head structures at the region of the implant, tors of the Wnt, BMP, Hh, and RTK pathways are less comprised mostly from cells of the host embryo. Thus, conserved, and found either in vertebrates or in Dro-cells from a specific region of the embryo can alter and sophila. It is probably easier to evolve novel inhibitors, reprogram cell differentiation and behavior in other re-because they should interact only with a limited domain gions of the embryo, implying that cells are normally of the protein they sequester. In addition, the generation communicating extensively during development, to ac-of new antagonists may provide novel regulatory fea-quire proper positional information. The dorsal blasto-tures that could not be adapted from existing modules. pore lip was consequently termed " the organizer, " and The inhibition of BMP signaling by Chordin in Xenopus its interaction with neighboring cells " induction. " Only is tightly regulated. Chordin, expressed on the dorsal in the last 20 years has it been possible to revisit the side, contains four cysteine-rich repeats, and can form system with new tools, including Drosophila develop-a complex with BMP. Chordin is antagonized by Xolloid, mental genetics, molecular genetic approaches in Xeno-a widely expressed metalloprotease that cleaves Chordin. pus, mouse genetics, chick transplantation and retrovi-Thus, Chordin levels remain high only near its source ral infections, and more recently utilization of zebrafish on the dorsal side of the embryo, and free BMP becomes genetics. available only on the ventral side. This system is highly A detailed knowledge of inductive developmental pro-conserved in flies and zebrafish. A new …