A research group at the Institute of Physical and Chemical Research, Cincinnati Children's Hospital in the United States, and Kyoto University has clarified the process of tracheal development and succeeded in developing a technique for producing tracheal tissue from mouse and human ES cells.
The normal development of mesenchyme, which produces cartilage and smooth muscle, is extremely important for the formation of the trachea, which is an essential organ for breathing.Until now, it was thought that the expression of the Nkx2.1 gene in epithelial tissue was required for the differentiation of mesenchyme, but in this study, first, even in mice lacking Nkx2.1, tracheal mesenchyme It was discovered that the expression of the Tbx4 gene, which is a marker for the disease, was observed.Instead, they found that the development of intertracheal mesenchyme requires activation of Wnt signaling in epithelial tissues, which is believed to regulate the expression of various genes.
We also discovered that activation of the Wnt signal in the epithelium followed by activation of the Wnt signal in the mesenchyme is also necessary for the expression of the Tbx4 gene and differentiation into the mesenchyme.The Tbx4 gene is expressed downstream of the Wnt ligand secreted in the epithelium, which activates the Wnt signal in the epithelium, and then the Wnt ligand secreted in the epithelium activates the Wnt signal in the epithelium. It is said that the outbreak is induced.It was revealed that such bidirectional Wnt signaling between epithelium and mesenchyme is the origin of tracheal development.
By applying this finding to the development of culture technology, the group also succeeded in inducing a complex tissue of intertracheal filling from mouse and human ES cells on a culture dish.The developed induction culture technology can be used as a clue for the development of an artificial mini-organ "organoid" that imitates an organ, so it can be expected to be applied to artificial respiratory formation technology in the future.In addition, since dysplasia of mesenchyme causes congenital respiratory diseases, it is expected that this result of elucidating the formation mechanism of mesenchyme will lead to the elucidation of these pathological conditions.
Paper information:[Nature Communications] Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells
