Katherine Rogers, a former student in our lab, and Nate have published a new paper in eLife called "Nodal patterning without Lefty inhibitory feedback is functional but fragile".
In this paper they investigate the role of feedback in development. Nodal is an important gene in early embryonic patterning that induces the expression of its own inhibitor, Lefty. Therefore, Nodal and Lefty form a feedback loop. To understand if such feedback is actually required during development, Katherine and Nate knocked out the lefty gene, which caused excess Nodal signaling, and then they bathed the embryos in a Nodal inhibitor drug, causing uniform inhibition. This allowed the removal of feedback, but maintained the appropriate amount of Nodal signaling. Under these conditions the embryos, remarkably, developed completely normally. Only when the embryos were provided with fluctuations in Nodal signaling did they begin to show defects, whereas normal embryos were able to buffer the fluctuations.
Thus, this study reveals that the embryo can undergo functional but fragile Nodal signaling without feedback.
Congratulations Katherine and Nate!