Download Project 7 - The Francis Crick Institute

Understanding the mechanisms behind congenital hearing loss: external ear canal
aplasia
Dr Barry Thompson (Francis Crick Institute Lincoln’s Inn Fields Laboratory), Dr Abigail Tucker (King’s
College London), Prof Dan Jiang (Guy’s & St Thomas’s NHS Trust, King’s College London).
Hearing as one of the five human senses plays a crucial role in our quality of life and integration into
society, impacting on speech and language skills. Congenital hearing loss has been estimated to occur
at an incidence of 1 in 1000 births, and as such has a major impact on the life of many children. Loss
of hearing can be due to defects in the external ear and ear canal; the middle ear, where sound waves
are amplified; and the inner ear, where hair cells process the sound waves and convert them to neural
inputs. This proposed project concentrates on the external ear. The external ear can be further
divided into the pinna (external ear flap), the external auditory meatus (EAM) (ear canal), and the
tympanic membrane (eardrum). During development the external auditory meatus invaginates into the
forming ear from the surface ectoderm, towards the condensing tympanic ring. Here it meets up with
the invaginating endodermal tissue of the forming Eustachian tube (tubotympanic recess) and middle
ear to form the tympanic membrane. Defects in formation of the external ear canal lead to a loss of
sound conduction and patients are subsequently deaf.
From research in the mouse it appears that the forming middle ear structures are central in controlling
the invagination of the EAM, with defects in the tympanic ring in particular being associated with
defects in the EAM (Mallo & Gridley, 1996). Similarly in patients, defects in the middle ear are often
associated with external ear defects (Bartel-Friedrich & Wulke, 2007).
Aims:
This project aims to understand the relationship between middle and external ear congenital
anomalies, and investigate the cell processes involved in external ear canal development.
The project combines an assessment of patient scans from the St Thomas’s External ear anomaly clinic
with analysis of embryonic external ear development using both mouse embryos and human tissue
provided by the Human Developmental Biology Resource. The project will combine expertise on ear
development from the lab of Dr Tucker (KCL), with the expertise of Dr Thompson (Crick) on epithelial
cell biology, and the clinical expertise of consultant otolaryngologist Prof Dan Jiang (St Thomas’s NHS
& KCL).
Anonymised scans from patients attending the St. Thomas’s External Ear clinic are available for
assessment. In particular the relationship of the bones of the middle ear and middle ear cavity to the
external canal defect will be assessed. The Tucker lab currently is registered with the Human
Developmental Biology Resource to be provided with human tissue for analysis of gene and protein
expression in the developing human ear. Using such tissue the cell dynamics during morphogenesis of
the EAM will be assessed and compared to similar staged tissue from the mouse.
Relevant references:
•Bartel-Friedrich S., Wulke, C. (2007). Classification and diagnosis of ear malformations. GMS Current topics in
orolaryngology - Head and Neck Surgery, 6: 1-21. •Lambert, P. R. and Dodson, E. E. (1996) 'Congenital
malformations of the external auditory canal', Otolaryngol Clin North Am 29(5): 741-60.
•Mallo, M. and Gridley, T. (1996) 'Development of the mammalian ear: coordinate regulation of formation of the
tympanic ring and the external acoustic meatus', Development 122(1): 173-9. •Nishizaki,N., Anniko, M., Orita, Y.,
Masuda, Y., Yoshino, T., Kanda, S., Sasaki, J. (1998). Programmes cell death in the development of the mouse
external auditory canal. Anatomical Record 252, 378-382.
•Thompson, H. Tucker , A.S. (2013). Dual origin of the epithelium of the middle ear. Science 339, 1453-1456.