Figure 2

Inhibition of the β-catenin/p300 interaction disrupts branching morphogenesis in mouse lung. (A) Lungs from embryonic mice treated with the β-catenin/p300 inhibiter IQ1 (right) or DMSO control (left) in utero. Pregnant mice received IQ1 (72 mg/kg/day) orally to expose the embryos to IQ1 in utero from E12.5 for 2 days (E12.5 + 2). The lungs of the embryos were dissected and the epithelium was stained with the ALP substrate NBT/BCIP. IQ1 decreased the size of the lung but elongated the airways. (B) Pregnant mice received IQ1 (72 mg/kg/day for low dose, 144 mg/kg/day for high dose) or ICG-001 (220 mg/kg/day) orally to expose the embryos in utero from E9.5 for 3 days (E9.5 + 3). IQ1 inhibited lung branching morphogenesis but ICG-001 did not. (C) H-E staining shows that IQ1 dilated the airways and decreased the density of mesenchymal cells. (D) E12.5 mouse embryonic lungs were cultured with either DMSO, IQ1 (10 μM) or ICG-001 (10 μM) for 24 hours and stained with ALP substrate NBT/BCIP. The arrows indicate new distal tips in DMSO and ICG-001 treated explants. IQ1 disrupted branching morphogenesis ex vivo. (E) IQ1 significantly decreased the number of the distal tips after 24 hour culture of E12.5 lungs. Data are mean ± SD from five lungs per group. *p < 0.025 vs. control by t-test.