DiGeorge syndrome and pharyngeal apparatus development

DiGeorge syndrome is the most frequent microdeletion syndrome in humans, and is characterized by cardiovascular, thymic and parathyroid, and craniofacial anomalies. The underlying cause is disturbed formation of the pharyngeal apparatus, a transient structure present during vertebrate development that gives rise to endocrine glands, craniofacial tissue, and the cardiac outflow tract. The pharyngeal apparatus is composed of derivatives of ectoderm, endoderm, mesoderm and the neural crest. Thus, complex interactions between cell types from different origins have to be orchestrated in the correct spatiotemporal manner to establish proper formation of the pharyngeal system. The analysis of engineered mouse mutants developing a phenotype resembling DiGeorge syndrome has revealed genes and signalling pathways crucial for this process. Intriguingly, these mouse models reveal that interference with either of two distinct phases of pharyngeal apparatus development can contribute to the aetiology of DiGeorge syndrome.