Middle ear development: Genetics and disease

The mammalian middle ear is composed of three bony ossicles, the malleus, incus, and stapes that function to conduct sound from the external to the inner ear. Normal development of middle ear structures is integral for transduction of sound, defects resulting in conductive deafness. Mice are reliant on both embryonic and postnatal developmental events to acquire hearing, and<br/>Eya1 mutant mice present with middle ear defects during both these developmental periods. Therefore, the aim of this project was to investigate the role of Eya1 in middle ear development and disease.<br/>Eya1 mutant mice on several backgrounds have previously been characterised with middle ear ossicle defects, however the role of Eya1 in regulating ossicle development has not been investigated. In this project, I characterise novel ossicle joint patterning defects of Eya1 mice of the C57BL/6 background, and show Eya1 to be expressed in the middle ear ossicles during embryonic development. I also investigate genetic regulators of joint development and show<br/>Gdf5 misexpression in the Eya1 +/- middle ear. I suggest Eya1 indirectly regulates middle ear joint patterning through a more general role in cartilage development. During postnatal development, Eya1 may further be required for the maintenance of joints. <br/>Transformation of Meckel’s cartilage results in separation of the jaw and middle ear, and is a characteristic feature of modern mammaliaforms. The Eya1 +/- mouse exhibits a delay in postnatal Meckel’s cartilage development, suggesting Eya1 as a regulator of this process. I investigate mechanisms associated with transformation of Meckel’s cartilage, and suggest Eya1 regulates this process indirectly through recruitment of TRAP positive cells.<br/>During adult stages of postnatal development, Eya1 +/- mice are predisposed to developing middle ear infections. With the use of microscopy and histological techniques, I characterise the Eya1 +/- mouse as a model of otitis media.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2013

Author dc:creator

• Joshi, Leena

Advisor dc:contributor.advisor

• Tucker, Abigail Saffron

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/1c50ca89-84f5-4011-a9a7-1707ec43ded1

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/1c50ca89-84f5-4011-a9a7-1707ec43ded1