King's College London

Research portal

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Research output: Contribution to journalArticle

Jacqueline M Tabler, William B Barrell, Heather L Szabo-Rogers, Christopher Healy, Yvonne Yeung, Elisa Gomez Perdiguero, Christian Schulz, Basil Z Yannakoudakis, Aida Mesbahi, Bogdan Wlodarczyk, Frederic Geissmann, Richard H Finnell, John B Wallingford, Karen J Liu

Original languageEnglish
Pages (from-to)623-635
Number of pages13
JournalDEVELOPMENTAL CELL
Volume25
Issue number6
DOIs
StatePublished - 24 Jun 2013

Documents

King's Authors

Abstract

Ciliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454