Effect of Mitogen-Activated Protein Kinase Kinase Inhibition on Apical Constriction and Differential Proliferation Rate in the Embryonic Chicken Lung

Abstract

This study investigates the role of two Mitogen-Activated Protein Kinase Kinase (MEK) inhibitors in the initiation and development of buds in the avian lung. The RAS-RAF-MEK-ERK pathway is complex, and many aspects of it are still insufficiently studied. A simplified description is that it consists of several protein kinases that catalyze the transfer of a phosphate group between molecules. The phosphate group eventually activates transcription factors in the nucleus, which leads to changes in gene expression.Previous research has shown that preventing apical constriction by inhibiting actomyosin contractility blocks branch initiation. It was also shown that inhibiting proliferation had no effect on the initiation of new branches. The researchers found that a combination of forces generated by apical constriction and epithelial cell proliferation is insufficient to fully shape the emerging lung bud. They concluded that the process was also affected by mechanisms in the mesenchyme that have not been sufficiently researched.Our study has found that even though lungs exposed to MEK inhibitors formed fewer and shorter branches, neither apical constriction, nor the rates of differential proliferation were affected. These results support the possibility that the mesenchyme has a physical role in the developing lung.