The ear canal is an open channel connecting the outside world to the middle ear; if the canal is absent or malformed, hearing is either restricted or lost. Treating ear canal defects is complicated by phenotypic variability and our still poor understanding of how the canal is built during development. Now, Abigail Tucker and colleagues address this shortfall with an analysis of human and mouse ear canal development. They first find that the ear canal forms in two distinct parts: the primary canal underlain by cartilaginous mesenchyme; and the meatal plug, a plate at the tip of the primary canal extending in to the middle ear. Each part has distinct proliferation patterns, suggesting different modes of growth. Once the meatal plug reaches the tympanic ring, the primary canal closes, becoming a continuous epithelial structure. Closure is associated with a loss of periderm by apoptosis, and when periderm is defective (in Grhl3 mutant mice), the ear canal prematurely closes. Re-opening of the canal epithelium occurs in a wave and is associated with loricrin expression, a marker of terminal differentiation of keratinocytes. Finally, the authors show how this developmental knowledge can be used to infer underlying mechanisms of ear canal defects in patients, such as canal aplasia (absence of ear canal) and canal atresia/stenosis (truncation/narrowing).
