Fishing the Molecular Bases of Treacher Collins Syndrome

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 2

PMID 22295061

Citations 20

Authors

Andrea M J Weiner

Nadia L Scampoli

Nora B Calcaterra

Affiliations

Soon will be listed here.

Abstract

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. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

Citing Articles

Deciphering TCOF1 mutations in Chinese Treacher Collins syndrome patients: insights into pathogenesis and transcriptional disruption.

Jiang Z, Mao K, Wang B, Zhu H, Liu J, Lang R Orphanet J Rare Dis. 2025; 20(1):57.

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Untangling Zebrafish Genetic Annotation: Addressing Complexities and Nomenclature Issues in Orthologous Evaluation of TCOF1 and NOLC1.

Hill-Teran G, Petrich J, Falcone Ferreyra M, Aybar M, Coux G J Mol Evol. 2024; 92(6):744-760.

PMID: 39269459 DOI: 10.1007/s00239-024-10200-0.

m hypomethylation as a mechanism for non-syndromic cleft lip and palate.

Alvizi L, Brito L, Kobayashi G, Bischain B, da Silva C, Ramos S Epigenetics. 2022; 17(13):2278-2295.

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Zebrafish Models for Human Skeletal Disorders.

Mari-Beffa M, Mesa-Roman A, Duran I Front Genet. 2021; 12:675331.

PMID: 34490030 PMC: 8418114. DOI: 10.3389/fgene.2021.675331.

Treacher Collins syndrome: Clinical report and retrospective analysis of Chinese patients.

Pan Z, Xu H, Chen B, Tian Y, Zhang L, Zhang S Mol Genet Genomic Med. 2020; 9(2):e1573.

PMID: 33332773 PMC: 8077114. DOI: 10.1002/mgg3.1573.

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