ZFIN ID: ZDB-PUB-180801-8
Scale-invariant patterning by size-dependent inhibition of Nodal signalling
Almuedo-Castillo, M., Bläßle, A., Mörsdorf, D., Marcon, L., Soh, G.H., Rogers, K.W., Schier, A.F., Müller, P.
Date: 2018
Source: Nature cell biology   20(9): 1032-1042 (Journal)
Registered Authors: Müller, Patrick, Schier, Alexander
Keywords: none
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*
PubMed: 30061678 Full text @ Nat. Cell Biol.
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.