Former PhD Student abstract: Maria Almuedo, PhD

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

Scale-invariant patterning guarantees the maintenance of tissue and organ proportions of individuals independently of changes in the size of the organism. We generated smaller zebrafish by removing 30% of their cells at 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 two hours after cell removal. Since 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 levels increased in smaller embryos, and embryos with reduced Lefty concentration 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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