Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Biophysics

Background:

• Understanding cell fate specification and morphogenesis is crucial in developmental biology.
• Gastruloids, stem cell models of postimplantation mammalian development, offer a unique platform to study these processes.
• The influence of physical parameters on developmental timing and outcomes is not fully understood.

Purpose of the Study:

• To investigate how physical parameters, specifically system size, impact morphogenetic timing and outcomes in gastruloids.
• To determine if transcriptional programs and cell fate composition are affected by variations in gastruloid size.
• To explore the adaptability of gastruloid models to different system sizes.

Main Methods:

• Quantitative live imaging of gastruloid development.
• Transcriptomic profiling to analyze gene expression patterns.
• Size perturbation experiments to assess system size effects.

Main Results:

• System size significantly affects morphogenetic timing, including symmetry breaking, multipolarity, and axial elongation.
• Transcriptional programs and cell fate composition remain largely stable across a broad range of gastruloid sizes.
• Extreme sizes exhibit distinct transcriptional modules and gene expression shifts, which can be rescued by size perturbation.
• Morphogenesis is driven by system size, demonstrating a decoupling of gene expression from morphogenetic progression in certain conditions.

Conclusions:

• Gastruloids are versatile models for studying spatiotemporal coordination in mammalian development.
• Physical constraints, particularly system size, play a critical role in modulating morphogenetic progression.
• The findings reveal how physical parameters can decouple gene expression programs from morphogenetic outcomes, offering insights into developmental plasticity.