PUBLICATION

Fishing the molecular bases of Treacher Collins syndrome

Authors
Weiner, A.M., Scampoli, N.L., and Calcaterra, N.B.
ID
ZDB-PUB-120202-16
Date
2012
Source
PLoS One   7(1): e29574 (Journal)
Registered Authors
Calcaterra, Nora
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cell Movement
  • Cell Size
  • Computational Biology
  • Disease Models, Animal*
  • Face/embryology
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Humans
  • Mandibulofacial Dysostosis/genetics*
  • Mandibulofacial Dysostosis/metabolism*
  • Mandibulofacial Dysostosis/pathology
  • Mice
  • Molecular Sequence Data
  • Neural Crest/metabolism
  • Neural Crest/pathology
  • Phenotype
  • Phosphoproteins/chemistry
  • Phosphoproteins/deficiency
  • Phosphoproteins/genetics*
  • Phosphoproteins/metabolism*
  • Sequence Homology, Amino Acid
  • Skull/embryology
  • Skull/metabolism
  • Time Factors
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed
22295061 Full text @ PLoS One
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.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping