Non-cell-autonomous role for Cripto in axial midline formation during vertebrate embryogenesis

Area of Science:

• Developmental Biology
• Molecular Biology
• Cell Signaling

Background:

• Membrane-associated proteins regulate morphogenetic signals during development.
• EGF-CFC family proteins, like Cripto, are glycosyl-phosphatidylinositol (GPI)-linked and crucial for transforming growth factor beta (TGFbeta) ligand Nodal activity.
• Nodal is a key factor in establishing the vertebrate body plan, with EGF-CFC proteins acting as cell-autonomous co-receptors.

Purpose of the Study:

• To investigate the in vivo function and signaling activity of the mammalian EGF-CFC protein Cripto during embryonic development.
• To determine if Cripto acts cell-autonomously or non-cell-autonomously during axial mesendoderm formation.
• To elucidate the role of Cripto in Nodal signaling and its impact on cell fate determination.

Main Methods:

• Phenotypic analysis of hypomorphic Cripto mutant mice.
• Chimeric analysis using Cripto null mutant cells.
• Gain-of-function experiments in chick embryos involving soluble Cripto protein exposure.

Main Results:

• Cripto is essential for the formation of notochordal plate, prechordal mesoderm, and foregut endoderm during mouse gastrulation.
• Cripto null mutant cells contributed to these tissues in chimeras, demonstrating non-cell-autonomous function.
• Soluble Cripto protein altered cell fates toward anterior mesendoderm in chick embryos, dependent on Nodal signaling.

Conclusions:

• Cripto functions non-cell-autonomously during axial mesendoderm formation in vivo.
• Cripto exhibits intercellular signaling activity, potentially acting as a secreted factor.
• Findings support a model where Cripto acts in trans to mediate Nodal signaling, influencing vertebrate body plan development.