Programmed cell death at the midline patterns ipsilateral gastrulation in the amniote

Bilaterality, is the predominant body plan in the animal kingdom. Cells either from the left or right side, rarely cross the body midline plane throughout life, as evidenced by naturally occurring bilateral gynandromorphs. However, it has been a longstanding mystery how this evolutionary conserved ipsilaterality is achieved in bilaterians, including humans. Using the chick embryo as a model, we show that extracellular matrix (ECM) and caspase-3-dependent programmed cell death (PCD) localize to the primitive streak (PS) midline. Both, faithfully direct ipsilateral ingression through the inhibition of contralateral cellular invasion. PS midline PCD is dependent on ECM accumulation. Suppression of these components results in contralateral cellular invasion. Remarkably, induced PCD alone, without ECM, is sufficient to rescue ipsilateral gastrulation. Our findings reveal that PCD actively patterns ipsilaterality, a hitherto unknown role for this basic developmental process