Cadherins modulate the self-organizing potential of pseudo-embryos

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Molecular Mechanisms

Background:

• Embryonic stem cells can form gastruloids, a 4D model for studying post-implantation embryonic patterning.
• Gastruloids exhibit self-organization, mimicking gastrulation-like processes and forming embryo-like patterns.

Purpose of the Study:

• To investigate the molecular and cellular mechanisms driving gastruloid self-organization.
• To understand the role of cadherin switching in embryonic stem cell patterning.

Main Methods:

• Studied molecular and cellular mechanisms in gastruloid formation.
• Investigated the role of E-cadherin and N-cadherin regulation by Snai1.
• Analyzed the impact of cadherin inactivation on gastruloid morphogenesis.

Main Results:

• Self-organization competence in gastruloids is linked to coordinated cadherin switching.
• Snai1-mediated repression of E-cadherin is critical, controlling pluripotency exit and E- to N-cadherin transition.
• N-cadherin inactivation promotes morphogenetic competence, leading to embryo-like structures with rostro-caudal somite patterning.

Conclusions:

• A molecular mechanism integrating pluripotency exit and differentiation pace drives gastruloid self-organization.
• Cadherin dynamics, particularly the E- to N-cadherin switch regulated by Snai1, are fundamental to embryonic patterning in gastruloids.