Retinoic Acid Receptor γ Activity Plays a Critical Role in Regulating Early Mouse Gastruloid Development.

Area of Science:

• Developmental Biology
• Molecular Biology
• Stem Cell Biology

Background:

• Regulation of all-trans retinoic acid (ATRA) signaling is critical for early embryonic development.
• Embryonic stem (ES) cell-derived gastruloids serve as a model for studying early developmental processes.
• The specific roles of retinoic acid receptor (RAR) α and γ in gastruloid development require further elucidation.

Purpose of the Study:

• To investigate the distinct roles of RARα and RARγ in ES cell-derived gastruloid development.
• To examine the spatial expression patterns of RARγ and its relationship with key developmental markers.
• To determine the effects of ATRA, RARα agonists, and RARγ agonists/antagonists on gastruloid morphogenesis.

Main Methods:

• ES cell-derived gastruloids were treated with ATRA, RARα agonists, RARγ agonists, and RARγ antagonists.
• Spatial expression of RARγ, Nanog, Sox2, Oct4, and Brachyury (TBXT) was analyzed.
• Effects on gastruloid symmetry-breaking and axial elongation were assessed.

Main Results:

• RARγ expression was restricted to primitive cells expressing ES cell and early progenitor markers.
• Treatment with ATRA or an RARγ agonist blocked gastruloid symmetry-breaking and axial elongation.
• RARα agonists showed a tendency to enhance axial elongation, unlike RARγ agonists.
• RARγ antagonists, at specific concentrations, induced multi-axis gastruloid elongations.

Conclusions:

• RARγ plays a critical and distinct role in regulating gastruloid development, particularly in establishing symmetry and axial elongation.
• The spatial restriction of RARγ expression suggests a specialized function in primitive progenitor populations.
• Differential activities of RARα and RARγ highlight their unique contributions to embryonic patterning.