Biomedical subjects

Jo-Maree Courtney

Publications and source records attributed to Jo-Maree Courtney.

4 recordsLinked to original sources

PubMed2005

The Ectodysplasin and NFkappaB signalling pathways in odontogenesis.

Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder affecting organs of ectodermal origin including teeth, hair and sweat glands. Defects in Ectodysplasin (tabby), Edar (downless) and Edar associated death domain (Edaradd) (crinkled) cause HED in both humans and mice. Ectodysplasin is a tumour necrosis factor (TNF) superfamily member whose downstream signalling is transduced by the inhibitor of kappaB kinase (IKK) complex and inhibitors of kappaB (IkappaB) to activate the transcription factor NFkappaB. NFkappaB signalling is involved in a wide range of cellular processes and at each stage the different family members must be tightly regulated for each function. Recent data have demonstrated the importance of this signalling pathway in odontogenesis, particularly in the formation of cusps. Here we review recent advances in our understanding of Ectodysplasin/NFkappaB signalling in tooth development and in particular the central role of the IKK complex.

Animals↗

PubMed2004

Traf6 is essential for murine tooth cusp morphogenesis.

Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.

Animals↗

PubMed2003

Expression of TNF-receptor-associated factor genes in murine tooth development.

Tumor necrosis factor receptor-associated factors (TRAFs) belong to a family of intracellular adaptor proteins that mediate signaling downstream of various cell surface receptors. We carried out comparative in situ hybridization analysis of five Traf genes Traf1, Traf2, Traf3, Traf4 and Traf6 during murine odontogenesis from the formation of the epithelial thickening to the early bell stage. Traf2, Traf3 and Traf6 showed weak expression in the thickened epithelium. Expression of Traf1, Traf2 and Traf6 were observed in the outer edges of the bud epithelium whereas Traf3 was strongly expressed at the tip of the bud epithelium. Expression of Traf1, Traf4 and Traf6 were detected in the dental papilla mesenchyme. Traf2 showed restricted expression in the internal enamel epithelium of the bell stage while expression of Traf1, Traf3, Traf4 and Traf6 were observed in both the internal and the external enamel epithelium. During early odontogenesis, all five genes show dynamic spatiotemporal expression patterns.

Animals↗

PubMed2001

The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function.

The mouse mutant ducky, a model for absence epilepsy, is characterized by spike-wave seizures and cerebellar ataxia. A mutation in Cacna2d2, the gene encoding the alpha 2 delta-2 voltage-dependent calcium channel accessory subunit, has been found to underlie the ducky phenotype. The alpha 2 delta-2 mRNA is strongly expressed in cerebellar Purkinje cells. We show that du/du mice have abnormalities in their Purkinje cell dendritic tree. The mutation in alpha 2 delta-2 results in the introduction of a premature stop codon and predicts the expression of a truncated protein encoded by the first three exons of Cacna2d2, followed by 8 novel amino acids. We show that both mRNA and protein corresponding to this predicted transcript are expressed in du/du cerebellum and present in Purkinje cells. Whereas the alpha 2 delta-2 subunit increased the peak current density of the Ca(V)2.1/beta(4) channel combination when co-expressed in vitro, co-expression with the truncated mutant alpha 2 delta-2 protein reduced current density, indicating that it may contribute to the du phenotype.

Alleles↗