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The mammalian trachea is patterned across the dorsal ventral axis. Smooth muscle is present in the dorsal aspect of the trachea while C shape cartilaginous rings are located in the ventral side. This arrangement allows flexibility during inspiration and prevents the collapse of the walls of the trachea during expiration.
It is unknown how tracheal patterning is established, moreover, the source of the progenitor cells that give rise to tracheal muscle or cartilage has not been identified. Disrupted tracheal patterning is observed in congenital defects such as airway malacia. In this condition, the walls of the trachea and bronchi are soft because of the lack of cartilage. Although the incidence of tracheomalacia is high (1:3000 live births), the etiology remains elusive.
Our goal is to define the molecular mechanisms underlying the patterning of the developing trachea and differentiation of tracheal chondrocytes and myocytes.
We are currently studying a model wherein conditional deletion of Wls (gene that encodes a protein involved in secretion of Wnt ligands) in epithelium of developing trachea results in mispatterning of tracheal mesenchyme with absence of cartilage and expansion of muscle into the ventral aspect of the trachea. These studies will provide critical knowledge about muscle and cartilage differentiation process, necessary for better diagnosis and treatment of diseases of the conducting airways.
This work is supported by a grant from the NIH-National Heart, Lung and Blood Institute.
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Sagittal sections of E14.5 mouse embryos are shown. In control embryos, the tracheal muscle, stained with S antibody, is located to the dorsal aspect of the trachea (A and B red); cartilage is present in the ventral side of the trachea and it was stained with Sox9 antibody (A green). The dorsal-ventral patterning is disrupted in the WlsShhCre mice. In these embryos, cartilage is absent while the muscle is expanded to ventral side of the trachea (C and D). Nkx2.1 antibody was utilized to stain the tracheal epithelium (B and D dark green). Dashed lines indicate dorsal side of the trachea. Schematics of tracheal cross sections depict the arrangement of cartilage and muscle in control (E) and expansion of muscle into the ventral side of trachea in Wls ShhCre mice. T: trachea.
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