Molecular Mechanisms of Primary Induction
Aaron B. Steiner, Mark J. Engleka, Qun Lu, Eileen C. Piwarzyk, Sergey Yaklichkin, Julie L. Lefebvre, James W.Walters, Liliam Pineda-Salgado, Patricia A. Labosky and Daniel S. Kessler 2006. FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development, Development 133, 4827-4838.
Briefly tell us a bit about yourself, your career path over the years, and specifically what led you to begin working on axis specification in Xenopus.
In this paper you used three main tools to manipulate the FoxD3 gene. They were specific morpholinos, and an activating VP16-FoxD3 and a repressing Engrailed-FoxD3 protein chimeras. Can you please compare the use of these tools, and describe how they suggest FoxD3 functions as a transcriptional repressor?
Pelmo Takza and Leslie Christensen
You favor a model in which FoxD3 is repressing a repressor of Nodal transcription. Can you please summarize the support for this model and mention whether the identity of this hypothesized Nodal repressor has been determined?
You state in your paper that “If FoxD3 were acting to relieve inhibition of Nodal ligand or signaling components, it is predicted that increased Nodal signaling activity would result in increased Nodal transcription by positive feedback”. Can you please explain the evidence for this and how such a positive feedback mechanism would work?
What do you think is acting upstream of FoxD3 leading to its expression? Is it the Nodal signaling pathway itself or another signaling pathway?
Can you describe the implications of the action of Nodal on Stem cells? Other studies have shown that Nodal is required to maintain the pluripotency of human embryonic stem cells, but that stem cells without nodal can also be established. Stem cells, however, require FoxD3. Do you have a theoretical model for how Nodal and FoxD3 function in maintaining pluripotency?
Currently in your opinion what are the most pressing questions in the field of mesoderm induction and axis specification? What steps are your lab taking to address those questions?