Research

A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle


Reference:

Dutton, K., Abbas, L., Spencer, J., Brannon, C., Mowbray, C., Nikaido, M., Kelsh, R. N. and Whitfield, T. T., 2009. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle. Disease Models & Mechanisms, 2 (1-2), pp. 68-83.

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Official URL:

http://dx.doi.org/10.1242/dmm.001164

Abstract

In humans, mutations in the SOX10 gene area cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

Details

Item Type Articles
CreatorsDutton, K., Abbas, L., Spencer, J., Brannon, C., Mowbray, C., Nikaido, M., Kelsh, R. N. and Whitfield, T. T.
DOI10.1242/dmm.001164
Uncontrolled Keywordstranscription factor sox10, inner-ear development, marie-tooth-disease, neural crest cells, stria vascularis, enteric nervous-system, hirschsprung-disease, b receptor gene, chronic intestinal pseudoobstruction, embryonic zebrafish
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code15288

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