Tags

Type your tag names separated by a space and hit enter

Treacher Collins syndrome: unmasking the role of Tcof1/treacle.
Int J Biochem Cell Biol 2009; 41(6):1229-32IJ

Abstract

Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. An animal model of the severe form of TCS, generated through mutation of the mouse homologue Tcof1 has recently revealed significant insights into the etiology and pathogenesis of TCS (Dixon and Dixon, 2004; Dixon et al., 2006; Jones et al 2008). During early embryogenesis in a TCS individual, an excessive degree of neuroepithelial apoptosis diminishes the generation of neural crest cells. Neural crest cells are a migratory stem and progenitor cell population that generates most of the tissues of the head including much of the bone, cartilage and connective tissue. It has been hypothesized that mutations in Tcof1 disrupt ribosome biogenesis to a degree that is insufficient to meet the proliferative needs of the neuroepithelium and neural crest cells. This causes nucleolar stress activation of the p53-dependent apoptotic pathway which induces neuroepithelial cell death. Interestingly however, chemical and genetic inhibition of p53 activity can block the wave of apoptosis and prevent craniofacial anomalies in Tcof1 mutant mice [Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33]. These findings shed new light on potential therapeutic avenues for the prevention of not only TCS but also other congenital craniofacial disorders which share a similar etiology and pathogenesis.

Authors+Show Affiliations

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19027870

Citation

Sakai, Daisuke, and Paul A. Trainor. "Treacher Collins Syndrome: Unmasking the Role of Tcof1/treacle." The International Journal of Biochemistry & Cell Biology, vol. 41, no. 6, 2009, pp. 1229-32.
Sakai D, Trainor PA. Treacher Collins syndrome: unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol. 2009;41(6):1229-32.
Sakai, D., & Trainor, P. A. (2009). Treacher Collins syndrome: unmasking the role of Tcof1/treacle. The International Journal of Biochemistry & Cell Biology, 41(6), pp. 1229-32. doi:10.1016/j.biocel.2008.10.026.
Sakai D, Trainor PA. Treacher Collins Syndrome: Unmasking the Role of Tcof1/treacle. Int J Biochem Cell Biol. 2009;41(6):1229-32. PubMed PMID: 19027870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treacher Collins syndrome: unmasking the role of Tcof1/treacle. AU - Sakai,Daisuke, AU - Trainor,Paul A, Y1 - 2008/11/05/ PY - 2008/08/18/received PY - 2008/10/28/revised PY - 2008/10/29/accepted PY - 2008/11/26/pubmed PY - 2009/10/27/medline PY - 2008/11/26/entrez SP - 1229 EP - 32 JF - The international journal of biochemistry & cell biology JO - Int. J. Biochem. Cell Biol. VL - 41 IS - 6 N2 - Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. An animal model of the severe form of TCS, generated through mutation of the mouse homologue Tcof1 has recently revealed significant insights into the etiology and pathogenesis of TCS (Dixon and Dixon, 2004; Dixon et al., 2006; Jones et al 2008). During early embryogenesis in a TCS individual, an excessive degree of neuroepithelial apoptosis diminishes the generation of neural crest cells. Neural crest cells are a migratory stem and progenitor cell population that generates most of the tissues of the head including much of the bone, cartilage and connective tissue. It has been hypothesized that mutations in Tcof1 disrupt ribosome biogenesis to a degree that is insufficient to meet the proliferative needs of the neuroepithelium and neural crest cells. This causes nucleolar stress activation of the p53-dependent apoptotic pathway which induces neuroepithelial cell death. Interestingly however, chemical and genetic inhibition of p53 activity can block the wave of apoptosis and prevent craniofacial anomalies in Tcof1 mutant mice [Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33]. These findings shed new light on potential therapeutic avenues for the prevention of not only TCS but also other congenital craniofacial disorders which share a similar etiology and pathogenesis. SN - 1878-5875 UR - https://www.unboundmedicine.com/medline/citation/19027870/Treacher_Collins_syndrome:_unmasking_the_role_of_Tcof1/treacle_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(08)00448-2 DB - PRIME DP - Unbound Medicine ER -