Cell death along the embryo midline regulates left–right sidedness

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Abstract
During embryogenesis, left–right sidedness is established by asymmetric expression of laterality genes. A recent model predicts the presence of a functional midline that divides the left side of the embryonic disc from the right side, separating left- and right-inducing signals. We show evidence that this midline is formed from a distinct population of cells within the primitive streak. Cells in the dorsal midline of the chick primitive streak display unique expression of the gastrulation markers fgf-8 and brachyury. These midline cells are fated to die, and dead cells remain in the midline during gastrulation. Inhibition of midline cell death compromises the early expression of laterality genes, such as shh and nodal and randomizes the direction of heart looping. We suggest that cell death along the primitive streak midline is a novel mechanism involved in the regulation of left–right asymmetry during early embryogenesis.