Tbx4-Fgf10 system controls lung bud formation during chicken embryonic development

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• The respiratory primordium's positioning and territory definition are critical early steps in lung development.
• The visceral mesoderm plays a key role in inducing respiratory endoderm formation and lung bud morphogenesis.

Purpose of the Study:

• To investigate the function of the T-box transcription factor Tbx4 in respiratory tract development.
• To elucidate the molecular mechanisms by which Tbx4 regulates lung bud formation and septation.

Main Methods:

• Ectopic expression of Tbx4 in the visceral mesoderm of the developing foregut using in ovo electroporation.
• Analysis of gene expression changes (Fgf10, Nkx2.1) and morphological outcomes, including bud formation and tracheo-esophageal septum development.

Main Results:

• Ectopic Tbx4 expression induced de novo lung bud formation in the esophagus by activating Fgf10.
• Interference with Tbx4 function led to failed lung bud formation and repressed Fgf10 expression.
• Tbx4 and Fgf10 induced ectopic Nkx2.1 expression in the esophageal endoderm, a marker for respiratory endoderm.
• Misexpression of Tbx4 disrupted the border of its expression domain, leading to failed tracheo-esophageal septum formation.

Conclusions:

• Tbx4 is a key regulator of multiple stages of respiratory tract development.
• Tbx4 controls initial endodermal bud formation, respiratory endoderm specification, and the critical septation process separating the airway from the esophagus.