Abstract
The first obvious sign of bilateral symmetry in mammalian and avian embryos is the appearance of the primitive streak in the future posterior region of a radially symmetric disc. The primitive streak marks the midline of the future embryo. The mechanisms responsible for positioning the primitive streak remain largely unknown. Here we combine experimental embryology and mathematical modelling to analyse the role of the TGFβ-related molecules BMP4 and Vg1/GDF1 in positioning the primitive streak. Bmp4 and Vg1 are first expressed throughout the embryo, and then become localised to the future anterior and posterior regions of the embryo, where they will, respectively, inhibit or induce formation of the primitive streak. We propose a model based on paracrine signalling to account for the separation of the two domains starting from a homogeneous array of cells, and thus for the topological transformation of a radially symmetric disc to a bilaterally symmetric embryo.
Highlights
How do vertebrate embryos break their initial radial symmetry and establish a midline as the axis of bilateral symmetry? In amphibians and fishes, the whole embryo is initially patterned by antagonistic gradients of BMP and Wnt/Nodal/Activin and BMP antagonists[1,2,3]
A bead of BMP4 placed in the posterior marginal zone (Fig. 1A) causes downregulation of Vg1 (23/26, control: 0/10) (Fig. 1B,C)
Vg1 downregulation was paralleled by inhibition of primitive streak formation: in 42/49 embryos incubated overnight after a posterior graft of a BMP4 bead, the primitive streak failed to form near the bead, but two streaks
Summary
How do vertebrate embryos break their initial radial symmetry and establish a midline as the axis of bilateral symmetry? In amphibians and fishes, the whole embryo is initially patterned by antagonistic gradients of BMP (ventrally) and Wnt/Nodal/Activin and BMP antagonists (dorsally)[1,2,3]. A bead of BMP4 placed in the posterior marginal zone (Fig. 1A) causes downregulation of Vg1 (23/26, control: 0/10) (Fig. 1B,C).
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