Cell death along the embryo midline regulates left-right sidedness

Kristine A. Kelly, Yan Wei, Takashi Mikawa

Developmental Dynamics Volume 224, Issue 2, Pages 238-244

nfig001.jpgFigure 1. Midline cells are molecularly specified before Hensen’s node formation. Expression of gastrulation genes fgf-8 (a,b,e,f,i,j) and brachyury (c,d,g,h,k,l) was examined with RNA in situ hybridization at the prestreak Hamburger and Hamilton (HH) stage 1(9) (a,c), the mid-streak HH stage 3 (b,d,e,g), and the definitive streak HH stage 4 (f,h). Note that only higher expression was selectively detected with submaximal color development. i-l: Transverse sections of e-h, respectively; Purple staining, the area positive for transcripts; arrows, the midline population exhibiting a unique expression pattern of gastrulation genes in the primitive streak midline; ps, primitive streak; hn, Hensen’s node; L and R, left and right sides of embryonic discs, respectively.

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.

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