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

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


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blastula / metabolism*
  • Body Patterning* / genetics
  • Gene Expression Regulation, Developmental
  • Left-Right Determination Factors / genetics
  • Left-Right Determination Factors / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Signal Transduction
  • Time Factors
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Left-Right Determination Factors
  • Lft2 protein, zebrafish
  • Membrane Proteins
  • Zebrafish Proteins
  • lft1 protein, zebrafish
  • nomo protein, zebrafish