Amnion signals are essential for mesoderm formation in primates

Area of Science:

• Developmental biology
• Genetics
• Stem cell biology

Background:

• Mammalian embryonic development shows conserved features but also gene divergence.
• The gene ISL1 is known for its role in heart development (cardiogenesis).

Purpose of the Study:

• To investigate the function of ISL1 in primate embryonic development.
• To understand the role of the amnion as a signaling center.

Main Methods:

• Generated a transcriptional atlas of over 30,000 cells from post-implantation non-human primate embryos.
• Utilized CRISPR/Cas9 gene editing to target ISL1 in non-human primate embryos.
• Conducted loss-of-function and rescue studies using human embryonic stem cells.

Main Results:

• ISL1 regulates a gene network in the primate amnion.
• Targeting ISL1 in non-human primates leads to embryonic lethality.
• Mutant embryos show failed mesoderm formation due to reduced BMP4 signaling from the amnion.
• ISL1 plays a similar role in human in vitro derived amnion.

Conclusions:

• ISL1 is essential for primate embryogenesis, particularly for mesoderm formation via amnion signaling.
• The amnion acts as a critical signaling center during primate mesoderm development.
• In vitro primate model systems are valuable for studying early human embryonic development genetics.