Defect-buffering cellular plasticity increases robustness of metazoan embryogenesis

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• Developmental processes exhibit robustness against genetic and environmental variations.
• The capacity of individual cells to adapt to genetic changes (phenotypic plasticity) during development is not fully understood.
• Systematic evaluation of cellular robustness and plasticity under genetic perturbations is needed.

Purpose of the Study:

• To systematically evaluate the robustness and phenotypic plasticity of individual developing cells in Caenorhabditis elegans under genetic perturbations.
• To quantify the phenotypic landscape of embryogenesis following large-scale gene knockdown.

Main Methods:

• Large-scale gene perturbation (individual knockdown of >750 conserved genes).
• Live imaging and lineage tracing.
• Single-cell phenomics to quantify phenotypic changes in >2,000 embryos.

Main Results:

• Cellular genetic systems are not universally robust to single-gene perturbations, with frequent cellular defects observed.
• Many cellular defects were transient, demonstrating phenotypic plasticity for alleviation, correction, and accommodation.
• Developmentally related cell modules may buffer positional changes, contributing to robustness.

Conclusions:

• Cellular plasticity is a significant factor in compensating for genetic perturbations during development.
• Multicellularity and coordinated cell modules contribute to developmental robustness.
• These findings highlight cellular plasticity and multicellularity as key compensatory strategies for robust development.