Restoration of polr1c in Early Embryogenesis Rescues the Type 3 Treacher Collins Syndrome Facial Malformation Phenotype in Zebrafish

Abstract

Treacher Collins syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects. Recently, the authors' group unfolded the pathogenesis of polr1c Type 3 TCS by using the zebrafish model. Facial development depends on the neural crest cells, in which polr1c plays a role in regulating their expression. In this study, the authors aimed to identify the functional time window of polr1c in TCS by the use of photo-morpholino to restore the polr1c expression at different time points. Results suggested that the restoration of polr1c at 8 hours after fertilization could rescue the TCS facial malformation phenotype by correcting the neural crest cell expression, reducing the cell death, and normalizing the p53 mRNA expression level in the rescued morphants. However, such recovery could not be reproduced if the polr1c is restored after 30 hours after fertilization.

Zebrafish Models for Human Skeletal Disorders

“…Models of these diseases have been obtained after perturbation of zebrafish gene orthologs. These are tcof1 ( Weiner et al, 2012 ; Terrazas et al, 2017 ; Gil Rosas et al, 2019 ), polr1c ( Lau et al, 2016 ; Noack Watt et al, 2016 ; Kwong et al, 2018 ), polr1d ( Noack Watt et al, 2016 ), and eftud2 ( Lei et al, 2017 ; Wu J. et al, 2019 ). Mutations in human POLR1A gene that cause the Cincinnati type of acrofacial dysostosis and in OFD1 gene that induce the orofaciodigital syndrome type I have also been modified to obtain models of diseases in group 34 ( Mortier et al, 2019 , Supplementary Table 1 ).…”

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