Coordination between endoderm progression and mouse gastruloid elongation controls endodermal morphotype choice.

Area of Science:

• Developmental biology
• Stem cell biology
• Organoid research

Background:

• Embryonic development exhibits remarkable robustness with minimal morphogenetic variability.
• In vitro embryo-like models and organoids often display significant tissue morphogenetic variability.
• The underlying reasons for this discrepancy in developmental robustness are not fully understood.

Purpose of the Study:

• To investigate the morphogenetic progression and divergence of definitive endoderm (DE) in mouse gastruloids.
• To identify key drivers of morphotype variability in DE development within gastruloids.
• To develop interventions for reducing variability and guiding morphotype choice in in vitro models.

Main Methods:

• Cataloging and statistically characterizing diverse DE morphologies in gastruloids.
• Developing predictive models for DE morphotype based on early expression and morphology data.
• Analyzing predictive models to pinpoint crucial factors influencing morphotype variability.

Main Results:

• Identified and statistically characterized distinct DE morphologies in mouse gastruloids.
• Created predictive models capable of forecasting DE morphotype from earlier measurements.
• Discovered two essential coordination mechanisms absent in in vitro models but vital for robust gut-tube formation.

Conclusions:

• The mouse gastruloid model offers insights into the robustness of embryonic development.
• Understanding variability drivers can lead to improved quality and usability of 3D embryo-like models.
• Identifying missing coordination factors is crucial for advancing in vitro developmental models.