De Robertis Research Lab

Welcome

Our group studies the molecular patterning mechanisms that control the evolution of the animal body plan. We have cloned several genes that code for secreted antagonists of growth factors that are used by embryonic cells to form morphogen gradients. These proteins control tissue differentiations in all bilateral animals.

In 1984 De Robertis, together with his close colleague the late Walter Gehring, isolated the first vertebrate development-controlling gene, now called Hox-C6. Hox genes encode DNA-binding proteins that determine the differentiation of cells along the antero-posterior body axis, both in fruit flies and vertebrates.

Since the 1990s the De Robertis lab has been carrying out the systematic dissection of the molecular mechanisms that mediate embryonic induction. In 1924 Hans Spemann and Hilde Mangold had identified a region of the amphibian embryo that was able to induce the formation of Siamese twins after transplantation. Our group isolated many secreted factors specifically expressed in this region, including Chordin, Cerberus, Frzb1, Angpl1, Bighead and others. Many of these are antagonists of growth factor pathways.

We found that Chordin, a protein secreted by dorsal cells in prodigious amounts, binds to Bone Morphogenetic Protein (BMP) growth factors in the extracellular space, facilitating their transport to the ventral side of the embryo, where Chordin is digested by the Tolloid protease, releasing BMPs for signaling. This flow of growth factors determines dorsal (back) to ventral (belly) tissue differentiations in most bilateral animals, such as fruit flies, spiders, early chordates and mammals. However, the Chordin/Tolloid/BMP axis was inverted during evolution between invertebrates and vertebrates.

Our Main Interest: Molecular Biology of Vertebrate Gastrulation

During early vertebrate development, coordinated movements of groups of cells lead to the formation of the three germ layers, the ectoderm, the mesoderm and the endoderm. This process is called gastrulation, and by the end of it the main regions of the embryo– head, trunk and tail – become determined. Our work is aimed at identifying the genetic mechanisms that direct the formation of the body plan in frog or mouse embryos.