Special Seminar – Dr. Harry McNamara, Princeton University

Symmetry breaking and self-organization of a body axis from mouse embryonic stem cells 

Abstract: 

During development, the embryo must break symmetry to form body axes and patterned tissue structures. Recent discoveries have revealed that stem cell aggregates can recapitulate developmental patterning and morphogenesis in vitro; however, it remains largely unknown how these ‘stembryos’ break symmetry in the absence of extrinsic patterning cues. The gastruloid is a stembryo model which self-organizes an anterior-posterior body axis in response to transient, spatially uniform stimulation of Wnt signaling activity. It has been proposed that a reaction-diffusion Turing instability polarizes Wnt activity in the gastruloid, thereby defining a posterior organizer.

We use synthetic “signal-recording” gene circuits to trace fate information encoded by signaling dynamics in the mouse gastruloid. We find that an ordered sequence of BMP, Nodal, and Wnt signaling states predict cells’ future position along the anterior-posterior (A-P) axis even before any of these morphogen signals are themselves polarized. Our data demonstrate A-P axial polarization does not require a biochemical Turing instability, but instead proceeds through a cell sorting mechanism which resoles early signaling variability into spatially separated anterior and posterior domains. Our study reveals how stem cells can self-organize a body axis without extrinsic patterning cues.