Fishing the molecular bases of Treacher Collins syndrome with zebrafish

WEINER, A. M. J.; SCAMPOLI, N. L.; ARMAS, P.; CALCATERRA, N. B.

Whasington

Simposio; 6th Brain Research Meeting: RNA-Binding Proteins and Neurological Diseases symposium; 2011

Society for Neuroscience

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. Most mutations generate a premature stop codon, suggesting that haploinsufficiency of TCOF1?s encoded protein, treacle, is the underlying cause of TCS. The zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. Here, we report the identification of a zebrafish gene named nucleolar and coiled-body phosphoprotein 1-like (nolc1l) as the TCOF1 ortholog. We cloned and analysed nolc1l expression during zebrafish embryonic development and detected a dynamic spatiotemporal pattern similar to that observed for Tcof1 in mouse. Moreover, knockdown of nolc1l expression adversely affects the development of the neural crest as well as its craniofacial derivatives, but has no effect on the formation of other embryonic structures. Together, these results demonstrate that we have identified and characterized the TCOF1 orthologous gene in zebrafish and, through a knockdown of its expression, generated a fish with TCS-like phenotypes that will be an interesting model for studying the embryonic development of the disease.