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Title: The role of Notch ligands in development of the inner ear
Author: Brooker, Rachael Helen
ISNI:       0000 0001 3481 4799
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
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The sensory epithelium of the inner ear consists of a mosaic pattern of hair cells separated from one another by supporting cells. The Notch signalling pathway is thought to establish this pattern through a process of lateral inhibition, and has recently been shown to have an early role in inducing sensory patch formation. Several Notch ligands are expressed in the developing sensory patch, but their respective functions in relation to the two roles of Notch signalling are not clear. This thesis examines the role of two of these Notch ligands, Deltal and Jaggedl, in the development of the inner ear using conditional knockout mice. The effect of loss of these ligands upon hair cell production is strikingly different. In the absence of Jaggedl, the total number of hair cells in the cochlea is strongly reduced (although the number of inner hair cells is roughly doubled). This supports the idea that Jaggedl is required for the early inductive function of Notch in specifying the sensory patches early in development. Jaggedl conditional knockout mice also exhibit a loss of several of the vestibular sensory patches, with the cristae being most severely affected. Expression of the CDK inhibitor p27Kip1 is lost in the mutant cochlea excess proliferation may thus explain the overproduction of inner hair cells. In the absence of Deltal, auditory hair cells are produced early and in excess, in agreement with the lateral inhibition hypothesis, but, surprisingly, supporting cells are also overproduced. Deltal conditional knockout mice also exhibit defects in the vestibular patches. The cristae appear normal, while the maculae are lost or reduced. These findings confirm that Notch signalling has two distinct functions in the inner ear, for which different ligands are primarily responsible.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available