ArticleNature communications2017
Developmental nonlinearity drives phenotypic robustness.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed.
- Mechanisms of Phenotypic Evolution from Molecules to Organisms: Integrating Evolutionary Biochemistry and Evolutionary Developmental Biology.Annual review of ecology, evolution, and systematics · 2026Article
- Navigating the window: structural bottlenecks in avian craniofacial integration revealed by the ontogenetic patterning of shape variance.bioRxiv : the preprint server for biology · 2026Article
- Using deep learning models as a genetic architecture for the simulation of breeding schemes.G3 (Bethesda, Md.) · 2026Article
- Cell differentiation can underpin the reproducibility of morphogenesis.PLoS computational biology · 2026Article
- Clinical,medRxiv : the preprint server for health sciences · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Positional programs in early murine facial development and their role in human facial shape variability.Nature communications · 2025Article
- Article
- Gene-environment interactions modulate the phenotype severity in mouse models of congenital craniofacial syndromes.The Journal of clinical investigation · 2025Article
- Article
- A quadratic paradigm describes the relationship between phenotype severity and variation.Nature communications · 2025Article
- Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Stereotyped Subclones Revealed by High-Density Single-Cell Lineage Tracing Support Robust Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb.JBMR plus · 2025Article
- Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division.PLoS biology · 2024Article
- Robustness quantification of a mutant library screen revealed key genetic markers in yeast.Microbial cell factories · 2024Article
- Article
- Rapid and biased evolution of canalization during adaptive divergence revealed by dominance in gene expression variability during Arctic charr early development.Communications biology · 2023Article
- Article
- Evolutionary mechanisms modulating the mammalian skull development.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Robustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The mechanisms that produce robustness are poorly understood. Nonlinearities are a ubiquitous feature of development that may link variation in development to phenotypic robustness. Here, we manipulate the gene dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate development. We demonstrate that variation in Fgf8 expression has a nonlinear relationship to phenotypic variation, predicting levels of robustness among genotypes. Differences in robustness are not due to gene expression variance or dysregulation, but emerge from the nonlinearity of the genotype-phenotype curve. In this instance, embedded features of development explain robustness differences. How such features vary in natural populations and relate to genetic variation are key questions for unraveling the origin and evolvability of this feature of organismal development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.