Molecular and Functional Divergence of Zebrafish Sox Paralogs Controlling Endoderm Formation and Left-Right...

Area of Science:

• Developmental Biology
• Evolutionary Biology
• Genetics

Background:

• Endoderm development is crucial for forming vital organs like the liver and pancreas.
• SOX17 is a key transcription factor for mammalian endoderm formation.
• Zebrafish possess paralogs Sox32 and Sox17, evolved from an ancestral sox17, with suggested functional similarities to mammalian SOX17.

Purpose of the Study:

• To functionally compare zebrafish Sox32 and Sox17 with mammalian SOX17.
• To investigate the molecular basis for functional divergence between Sox32 and Sox17.
• To understand the evolutionary changes in these transcription factors impacting endoderm and left-right patterning.

Main Methods:

• Utilized early zebrafish embryos for functional testing.
• Employed hybrid protein functional analyses.
• Examined conserved peptide sequences in transcription factor domains.

Main Results:

• Human SOX17 could not induce endoderm specification in zebrafish, unlike Sox32.
• Sox32's specificity for the endoderm gene regulatory network is linked to divergence in its High Mobility Group domain.
• Changes in the C-terminal regions of Sox32 and Sox17 explain their differing target specificities.
• Specific conserved peptides in the Sox17 C-terminal domain are essential for organ asymmetry.

Conclusions:

• Sox32 and Sox17 exhibit distinct functions in zebrafish endoderm development and left-right patterning.
• Evolutionary alterations in specific domains of Sox32 and Sox17 are critical for their divergent roles.
• This study illuminates the molecular mechanisms underlying the functional evolution of these key developmental transcription factors.