Tags

Type your tag names separated by a space and hit enter

Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome.
Hum Mol Genet 2000; 9(10):1473-80HM

Abstract

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells.

Authors+Show Affiliations

School of Biological Sciences and Department of Dental Medicine and Surgery, University of Manchester, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10888597

Citation

Dixon, J, et al. "Increased Levels of Apoptosis in the Prefusion Neural Folds Underlie the Craniofacial Disorder, Treacher Collins Syndrome." Human Molecular Genetics, vol. 9, no. 10, 2000, pp. 1473-80.
Dixon J, Brakebusch C, Fässler R, et al. Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome. Hum Mol Genet. 2000;9(10):1473-80.
Dixon, J., Brakebusch, C., Fässler, R., & Dixon, M. J. (2000). Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome. Human Molecular Genetics, 9(10), pp. 1473-80.
Dixon J, et al. Increased Levels of Apoptosis in the Prefusion Neural Folds Underlie the Craniofacial Disorder, Treacher Collins Syndrome. Hum Mol Genet. 2000 Jun 12;9(10):1473-80. PubMed PMID: 10888597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome. AU - Dixon,J, AU - Brakebusch,C, AU - Fässler,R, AU - Dixon,M J, PY - 2000/7/11/pubmed PY - 2000/9/9/medline PY - 2000/7/11/entrez SP - 1473 EP - 80 JF - Human molecular genetics JO - Hum. Mol. Genet. VL - 9 IS - 10 N2 - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/10888597/Increased_levels_of_apoptosis_in_the_prefusion_neural_folds_underlie_the_craniofacial_disorder_Treacher_Collins_syndrome_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/9.10.1473 DB - PRIME DP - Unbound Medicine ER -