http://dx.doi.org/10.1016/j.bbadis.2016.03.005">
 

Document Type

Journal Article

Department/Unit

Department of Biology

Title

Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model

Language

English

Abstract

© 2016 Elsevier B.V. Treacher Collins Syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects, including the downward slanting palpebral fissures, hypoplasia of the facial bones, and cleft palate (CP). Over 90% of patients with TCS have a mutation in the TCOF1 gene. However, some patients exhibit mutations in two new causative genes, POLR1C and POLR1D, which encode subunits of RNA polymerases I and III, that affect ribosome biogenesis. In this study, we examine the role of POLR1C in TCS using zebrafish as a model system. Our data confirmed that polr1c is highly expressed in the facial region, and dysfunction of this gene by knockdown or knock-out resulted in mis-expression of neural crest cells during early development that leads to TCS phenotype. Next generation sequencing and bioinformatics analysis of the polr1c mutants further demonstrated the up-regulated p53 pathway and predicted skeletal disorders. Lastly, we partially rescued the TCS facial phenotype in the background of p53 mutants, which supported the hypothesis that POLR1C-dependent type 3 TCS is associated with the p53 pathway.

Keywords

Cleft palate, Craniofacial development, Disease model, Transcritpomic

Publication Date

2016

Source Publication Title

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Volume

1862

Issue

6

Start Page

1147

End Page

1158

Publisher

Elsevier

ISSN (print)

09254439

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