Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis

Area of Science:

• Developmental Biology
• Molecular Embryology
• Cell Signaling

Background:

• Xenopus nodal-related factors (Xnrs) are known mesoderm inducers.
• Activin signaling is upstream of Xnr transcription, suggesting a relay mechanism.

Purpose of the Study:

• To investigate the role of Xnr signaling in early amphibian embryogenesis using a dominant-negative mutant.
• To clarify the relationship between activin and Xnrs in mesoderm and endoderm induction.

Main Methods:

• Utilized a dominant-negative cleavage mutant of Xnr2 (cmXnr2) for loss-of-function experiments.
• Assessed mesoderm and endoderm induction by Xnr and activin RNA/protein.
• Analyzed effects on gastrulation, dorsal lip formation, and expression of dorsoanterior endoderm markers.

Main Results:

• cmXnr2 blocked Xnr-induced mesoderm induction but not activin RNA induction.
• cmXnr2 suppressed activin protein-induced mesoderm and endoderm induction, indicating interference with induced Xnr peptides.
• cmXnr2 expression rescued hyperdorsalization and gastrulation defects caused by Xnr2.
• cmXnr2 led to delayed dorsal lip formation and anterior truncations, with suppressed dorsoanterior endoderm marker expression.
• Xnr2 induced head organizer markers (cerberus, Xhex-1, Frzb) in animal caps.
• Head mesendoderm migration was reduced in cmXnr2-injected embryos.

Conclusions:

• Xnrs play essential roles in initiating gastrulation and establishing head organizer activity.
• Xnr signaling acts downstream of activin-like pathways in dorsal mesendodermal specification.
• A specific antagonistic relationship exists between Xnr2 and its dominant-negative mutant (cmXnr2).