Edwin Ferguson, Ph.D.

Pattern Formation During Early Embryogenesis; Role of dpp in Drosophila Embryo

Research Summary

In both arthropods and vertebrates, activity gradients of specific TGF-â family members, Dpp in Drosophila and BMP4 in Xenopus, specify positional information along the embryonic dorsal-ventral (D/V) axis. We are analyzing the DPP signal transduction pathway genetically and molecularly. We had previously identified the SMAD4 ortholog, Medea, by isolating mutations that act as dominant enhancers of a weak allele of a target gene of Dpp signaling. We have now extended this analysis by obtaining suppressors of a weak Medea allele, and shown that one class of these suppressors encodes an ubiquitin ligase, called D-Smurf, that ubiquitinates Smad proteins, thus targeting them for degradation. Loss of D-Smurf activity is lethal, and this lethality can be suppressed by mutations that reduce Dpp signaling. We are currently obtaining suppressors of D-Smurf lethality, and we hope that these mutations could identify novel positive-regulatory components of Dpp signaling. In a separate but related project done in collaboration with the laboratory of Dr. Anthony Mahowald, we are attempting to culture Drosophila germ line stem cells (GLSCs). Work from another lab indicated that Dpp acts as a signal within an "environmental niche" to maintain the GLSCs in a stem-cell fate. We are developing a system for the conditional activation and/or repression of Dpp signaling in the GLSCs. If perfected, this system could allow us to study the process of stem-cell maintenance and differentiation on a pure population of stem cells in vitro.

Selected Papers