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Nat Cell Biol. 2018 Sep;20(9):1032-1042. doi: 10.1038/s41556-018-0155-7. Epub 2018 Jul 30.

Scale-invariant patterning by size-dependent inhibition of Nodal signalling.

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Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Sevilla, Spain.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.


Individuals can vary substantially in size, but the proportions of their body plans are often maintained. We generated smaller zebrafish by removing 30% of their cells at the blastula stages and found that these embryos developed into normally patterned individuals. Strikingly, the proportions of all germ layers adjusted to the new embryo size within 2 hours after cell removal. As Nodal-Lefty signalling controls germ-layer patterning, we performed a computational screen for scale-invariant models of this activator-inhibitor system. This analysis predicted that the concentration of the highly diffusive inhibitor Lefty increases in smaller embryos, leading to a decreased Nodal activity range and contracted germ-layer dimensions. In vivo studies confirmed that Lefty concentration increased in smaller embryos, and embryos with reduced Lefty levels or with diffusion-hindered Lefty failed to scale their tissue proportions. These results reveal that size-dependent inhibition of Nodal signalling allows scale-invariant patterning.

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