TALE-family homeodomain proteins regulate endodermal sonic hedgehog expression and pattern the anterior endoderm

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Sonic hedgehog (Shh) is vital for anterior endoderm patterning and repressing pancreas gene expression.
• The precise regulatory pathway controlling endodermal Shh expression remains largely unknown.

Purpose of the Study:

• To elucidate the pathway controlling endodermal Shh expression.
• To investigate the role of Meis3 and its cofactor Pbx4 in endoderm development and patterning.

Main Methods:

• Utilized zebrafish embryos for in vivo studies.
• Employed dominant-negative constructs and antisense morpholino oligos (MOs) to disrupt Meis3 and Pbx4 function.
• Analyzed gene expression patterns, including insulin and Shh, using molecular techniques.

Main Results:

• Meis3 expression in endoderm correlates with Shh expression.
• Disruption of Meis3 or Pbx4 leads to ectopic insulin expression in the anterior endoderm.
• Meis3 is essential for maintaining endodermal Shh expression, acting upstream of Shh.
• Loss of Meis3 or Pbx4 causes anterior displacement of endoderm-derived organs due to pharyngeal region underdevelopment.

Conclusions:

• Meis3 and Pbx4 act in a complex within the endoderm to regulate Shh expression.
• This regulatory axis is critical for restricting insulin expression and proper patterning and growth of the foregut.
• The findings reveal a novel mechanism controlling anterior endoderm development in zebrafish.