Abstracts of papers presented at the 26th Genetics Societys Mammalian Genetics and Development Workshop held at the Institute of Child Health University College London on 20th November 2015.

摘要

Craniosynostosis is a common feature of craniofacial birth defects. It is characterised by premature fusion of the cranial sutures in the developing calvarium. One of the causes of craniosynostosis is associated with pathogenic FGFR2 signalling, and is caused by mutations in the gene which are thought to be activating in nature. In particular, mutations in the IIIc isoform (e.g. FGFR2c-C342Y) contribute to several craniofacial abnormalities including human Crouzon syndrome. However, little is known about how FGFR2c signalling regulates suture patency. This study aims to uncover the downstream effects of pathogenic FGFR2c signalling involved in craniofacial abnormalities using two mouse models. To address its role in calvarial development, conditional overexpression of Fgfr2c in a novel transgenic mouse reveals bones derived from the neural crest lineage were reduced in size. Contrary to expectations, craniosynostosis was absent. Moreover, these mutants exhibit global skeletal hypoplasia and cleft palate. The complexities of FGFR2c signalling highlight the need to uncover novel downstream targets. Ongoing work includes RNAseq transcriptome analysis of coronal sutural mesenchyme acquired using laser captured microdissection from the Crouzon mouse. Uncovering novel biomarkers will therefore improve the aetiology of FGF signalling in normal craniofacial development and its related pathologies.