Learning Objectives: The lining of the middle ear is of dual origin formed from the neural crest and endoderm in different parts of the cavity The pars flaccida is not formed from endoderm but neural crest and ectoderm The different tissues of the ear respond differently to ear infection Lineage tracing experiments in the mouse can shed light on the origin of cholesteatomas

The mammalian middle ear is a complex air-filled space housing the three middle ear ossicles, which transfer sound from the ear-drum to the inner ear. Recent lineage tracing experiments in the mouse have shown that during development this air filled space is created by the neural crest mesenchyme around the ossicles retracting back and transforming into an epithelium lining the roof (attic) and side (promontory) of the newly formed cavity. The rest of the cavity (hypotympanum) is lined by endoderm, continuous with the oral cavity via the Eustachian tube. The endoderm-derived epithelium is covered in a thick lawn of cilia, while the neural crest derived epithelial cells have a much simpler morphology. This dual origin extends to the tympanic membrane, where lineage tracing of the pars flaccida shows no endodermal contribution. This dual origin appears to be unique to mammals, evolving with the three ossicle middle ear. Defects in the cavitation process lead to defective barrier formation, leaving the middle ear susceptible to the development of middle ear problems such as otitis media and Cholesteatoma. In mice with otitis media the neural crest epithelium breaks down while the endodermally derived epithelium undergoes hyperplasia but retains much of its barrier function. We are interested in using our knowledge of the development of the ear using transgenic mice to try and identify the origins of high susceptibility to middle ear disease.