Abrupt suppression of NODAL signaling triggers primitive streak regression and axial body formation in amniote embryos
The primitive streak (PS) is a defining feature of early bird and mammal embryonic development, where cells internalize and differentiate into germ layers during gastrulation. In a subsequent phase, the streak regresses, laying down in its wake the progenitors of the post-cranial (axial) body, including the vertebrae, spinal cord, and limbs. However, how the PS initiates its regression and concomitantly transitions from generating primary germ layers to producing axial body progenitors remains unknown. Here, using live imaging, quantitative analysis, functional perturbations, and single-cell RNA sequencing in avian embryos, we show that PS formation and regression involve similar cellular dynamics, differing mainly in the fates adopted upon cell internalization, with NODAL signaling playing a pivotal role in this process. While NODAL signaling drives mesendoderm specification during gastrulation, its abrupt downregulation initiates streak regression and specification of axial body progenitors. Modulating NODAL activity is sufficient to delay or trigger this transition, effectively extending or terminating gastrulation. To test whether this mechanism is conserved in reptiles, which have been reported to lack a PS, yet are capable of extensive axial elongation, we examined turtle and snake embryos. We find indeed that a regressing PS forms in these species, that it accompanies axial body formation, and that its emergence coincides with the termination of NODAL expression. Our findings identify gastrulation and axial body formation as distinct developmental modules, with the shutdown of NODAL signaling at the PS acting as a conserved regulatory switch between them. We propose that the PS is a conserved structure required for axial body formation across amniotes that may have been co-opted for avian and mammalian gastrulation. Altogether, this work clarifies the regulatory mechanisms underlying the emergence of the axial body plan, sheds light on the evolutionary origin of PS formation, and may have applications in the engineering of early embryonic cell types.