BMP Antagonists in Spemann's Organizer Cooperate to Define Dorsal Cell Fates

Joanna Yeh
University of California, Berkeley

In 1924 Hans Spemann and his student Hilde Mangold conducted the famous “Organizer” experiment, which defined a region of the embryo that can induce specific cellular fates. They found that during normal amphibian development, a region on the dorsal side of the embryo initiates gastrulation, a complex series of cellular movements that ultimately defines the axis of the embryo. By transplanting the dorsal blastopore lip onto the ventral side of another host embryo, Spemann and Mangold showed that the transplant could initiate gastrulation movements and induce an entire additional dorsal side with head and tail structures, thus forming a “Siamese twin” embryo. It was shown that the host cells had been induced and organized by the dorsal blastopore lip to form dorsal structures when their fate would have otherwise been of ventral types. This dorsal blastopore lip was named the “Organizer” because of its abilities to initiate gastrulation and induce dorsal mesoderm and ectoderm from host tissues.

Since Spemann first described the properties of the Organizer, scientists have identified genes that are expressed in the dorsal blastopore lip that have organizing activity. These molecules fall into two categories: BMP and Wnt antagonists. Despite extensive scientific research, a signaling molecule or a group of molecules required for all of the inductive events in the Organizer has not yet been identified.

Using morpholino oligonucleotide (MO) technology in Xenopus tropicalis, I show that BMP antagonism is required for the activity of Spemann’s organizer. By reducing three BMP antagonists, Chordin, Noggin, and Follistatin, all at once, I show that dorsal tissues like neural, notochord, and somites are either entirely lost or greatly reduced. In addition, ventral tissues are significantly expanded. However, initial dorsal specification by the Nieuwkoop center remains intact so that only downstream signaling components of the Organizer are affected rather than the initial Organizer itself. Therefore, I conclude that BMP antagonism is required for the activity of Spemann’s Organizer and that Chordin, Noggin and Follistatin play redundant roles to specify dorsal cell fate.