Roles and Regulation of the Hippo Signaling Pathway in Mammalian Preimplantation Development

Area of Science:

• Developmental Biology
• Cell Signaling
• Genetics

Background:

• Mammalian embryos develop into blastocysts during preimplantation development.
• The Hippo signaling pathway plays crucial roles in mouse embryonic development.
• The TEA domain transcription factor 4 (TEAD4)-Yes-associated protein (YAP) complex is key in trophectoderm (TE) and inner cell mass (ICM) fate determination.

Purpose of the Study:

• To elucidate the multifaceted roles of the Hippo signaling pathway in mammalian preimplantation development.
• To detail the mechanisms regulating YAP, a central component of the Hippo pathway.
• To explore the evolutionary conservation of Hippo pathway functions in TE fate regulation.

Main Methods:

• Review of existing literature on Hippo signaling in mammalian embryogenesis.
• Analysis of YAP regulation mechanisms, including adherens junctions, cell polarization, and apical domain.
• Investigation of additional modulators like ROCK, TFAP2C, AMOT, RHO, mechanical forces, and metabolism.

Main Results:

• Hippo signaling, particularly TEAD4-YAP, governs TE and ICM cell fate.
• YAP is primarily regulated by adherens junctions (activation) and cell polarization/apical domain (inhibition).
• Other factors like ROCK, TFAP2C, AMOT, RHO, mechanical cues, and metabolism also modulate Hippo signaling and YAP activity.

Conclusions:

• The Hippo pathway regulates diverse embryonic processes, including zygotic gene activation, cell state transitions, and epiblast maturation.
• TE fate regulation by the Hippo pathway is conserved in human and bovine embryos, though species-specific differences exist.