• Tracheal Patterning

    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 the tracheal pattern 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. Similarly, other conditions such as complete tracheal rings are also the result of abnormal tracheal patterning; however, the underlying molecular mechanisms causing the condition are unknown. 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 mispattterning 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-NHLBI.
  • Immunofluorescence staining of a mouse embryo cross section depicts the normal dorsal ventral patterning of the supporting structures of the trachea. Deviations to this pattern result in conditions such as tracheomalacia and complete tracheal rings. Sox9 staining identifies the region where cartilage will develop. SMA stained cells will give rise to trachealis muscle.

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