Submucosal gland development in the airway is controlled by lymphoid enhancer binding factor 1 (LEF1)

Area of Science:

• Developmental Biology
• Molecular Biology
• Respiratory System Research

Background:

• Previous studies indicated lymphoid enhancer binding factor 1 (Lef1) gene transcription increases before airway submucosal gland formation.
• The precise role of LEF1 in initiating and supporting airway submucosal gland development remained unclear.

Purpose of the Study:

• To functionally investigate the necessity and sufficiency of LEF1 in airway submucosal gland development.
• To explore LEF1's role in initiating and supporting gland formation in the nasal and tracheal mucosa.

Main Methods:

• Utilized Lef1-deficient mice and ferret xenograft models with antisense oligonucleotides to assess LEF1 requirement.
• Employed recombinant adeno-associated virus and transgenic mice for ectopic LEF1 overexpression studies in human and mouse airway models.

Main Results:

• LEF1 deficiency or inhibition prevented submucosal gland formation in mouse and ferret airway models.
• Ectopic overexpression of LEF1 in human bronchial and mouse airway xenografts did not induce new submucosal gland development.

Conclusions:

• LEF1 is functionally required for the initiation and morphogenesis of airway submucosal glands.
• LEF1 expression alone is insufficient to induce submucosal gland development, indicating other factors are necessary.