Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression...

Area of Science:

• Developmental Biology
• Evolutionary Biology
• Genetics

Background:

• Eomesodermin (Eomes) is a crucial T-box transcription factor in vertebrate embryonic development and the immune system.
• Mammalian Eomes mutants show early lethality, contrasting with zebrafish lacking Eomesa, suggesting evolutionary divergence in function or molecular context.
• Investigating Eomes conservation and functional divergence across species is key to understanding developmental processes.

Purpose of the Study:

• To compare the molecular function and evolutionary conservation of Eomesodermin (Eomes) between mammals and zebrafish.
• To investigate the role of zebrafish Eomesa and other T-box factors in early development and left-right asymmetry.
• To elucidate the regulatory mechanisms of Eomesa in zebrafish left-right organizer formation.

Main Methods:

• Analysis of distinct Eomes isoforms in mouse cell types.
• Functional comparison of murine Eomes isoforms and zebrafish Eomesa.
• Examination of zebrafish Eomesa, Eomesb, and Tbx16 functions, including interactions with Mixl1 and Gata5.
• Assay of T-box factors' ability to induce zebrafish left-right organizer progenitors and modulate vgll4l expression.

Main Results:

• No evidence of functional divergence was found between murine Eomes isoforms and zebrafish Eomesa.
• Functional redundancy was observed between zebrafish Eomesa and Tbx16, though Tbx16 did not synergize with Mixl1 and Gata5.
• Zebrafish Eomesa indirectly upregulates vgll4l via feedforward loops, indicating a role in left-right asymmetry establishment.
• Other T-box factors could not induce left-right organizer progenitors like Eomesa.

Conclusions:

• Eomesodermin (Eomes) exhibits conserved molecular function across vertebrates, participating in similar developmental processes.
• Differential requirements for Eomes in teleosts are attributed to co-expressed T-box factors with distinct molecular capabilities.
• Eomesa plays a significant role in the formation of the zebrafish left-right organizer.