Proteostasis governs differential temperature sensitivity across embryonic cell types.

Area of Science:

• Developmental biology
• Genomics
• Stress biology

Background:

• Embryonic development exhibits robustness but can be compromised by environmental stressors like temperature.
• Specific cell types display varying sensitivity to stress, yet the underlying mechanisms remain unclear.

Purpose of the Study:

• To identify cell types and molecular pathways responsible for phenotypic variability in zebrafish embryos under temperature stress.
• To investigate the cellular and molecular basis of temperature sensitivity during embryonic development.

Main Methods:

• Whole-animal single-cell RNA sequencing (scRNA-seq) was employed on hundreds of individual zebrafish embryos exposed to temperature stress.
• Analysis focused on identifying perturbed cell type proportions, altered gene expression programs, and developmental timing asynchrony.

Main Results:

• Temperature stress altered cell type proportions and gene expression profiles across numerous cell types.
• Developmental timing became asynchronous under thermal stress.
• Notochord sheath cells were identified as particularly temperature-sensitive, accumulating misfolded proteins and causing structural notochord failure and anatomical defects.

Conclusions:

• Whole-animal scRNA-seq is a powerful approach to uncover mechanisms of developmental robustness and identify critical cellular failure points.
• Notochord sheath cell sensitivity to temperature-induced protein misfolding represents a key vulnerability in embryonic development.