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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.

Author information

1
Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.
2
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Sevilla, Spain.
3
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
4
Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany. patrick.mueller@tuebingen.mpg.de.

Abstract

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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PMID:
30061678
PMCID:
PMC6217922
[Available on 2019-01-30]
DOI:
10.1038/s41556-018-0155-7

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