Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos.

A challenge in cumulative risk assessment is to model hazard of mixtures. EFSA proposed to only combine chemicals linked to a defined endpoint, in so-called cumulative assessment groups, and use the dose-addition model as a default to predict combined effects. We investigated the effect of binary mixtures of compounds known to cause craniofacial malformations, by assessing the effect in the head skeleton (M-PQ angle) in 120hpf zebrafish embryos.

Gene expression profiling in the developing secondary palate in the absence of Tbx1 function.

Background: Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, including disruption of the cardiac outflow tract, thymic/parathyroid aplasia and cleft palate. Amongst the genes within this region, TBX1 is a major candidate for many of these developmental defects. Targeted deletion of Tbx1 in the mouse has provided significant insight into the function of this transcription factor during early development of the cardiac and pharyngeal systems.

Zebrafish as an Alternative Vertebrate Model for Investigating Developmental Toxicity-The Triadimefon Example.

Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in several model organisms and in humans. The present study evaluated in detail the developmental effects seen in zebrafish embryos exposed to triadimefon, confirmed and expanded upon previous phenotypic findings and compared them to those observed in other traditional animal models. In order to do this, we exposed embryos to 2 and 4 µg/mL triadimefon and evaluated growth until 120 h post-fertilization (hpf) through gross morphology examination.

Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors.

TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorge syndrome.

Tooth development: 2. Regenerating teeth in the laboratory.

Tooth loss can occur for a number of reasons and a variety of prosthetic tooth replacement solutions are available to the dental practitioner. This article discusses current approaches in the use of tissue engineering to replace teeth or repair dental tissues. These strategies will depend upon the manipulation of stem cells in the laboratory and, whilst much progress has recently been made, it is likely that successful human tooth regeneration is still some years ahead.

Expression of the Scube3 epidermal growth factor-related gene during early embryonic development in the mouse.

Scube genes encode a small group of secreted plasma membrane-associated proteins characterised by a N-terminal signal peptide sequence, multiple EGF domains, a N-linked glycosylated spacer region and a C-terminal CUB region. Here we describe expression of the mouse Scube3 gene during early embryonic development. Transcripts were initially localised to neurectoderm of the developing embryo, in the ventral rhombencephalon and caudal neuropore.

Tooth development: 1. Generating teeth in the embryo.

Teeth are organs that develop in the embryo via a series of interactions between oral epithelium and neural crest-derived ectomesenchyme of the early jaws. These interactions are initiated by the regional production of signalling molecules in the oral epithelium and the transfer of information to the underlying mesenchyme via homeobox gene transcription. This article describes how these interactions are co-ordinated in the embryo during development of the dentition and provides a theoretical basis for the second article in this series; understanding how biologists are attempting to generate teeth artificially in the laboratory.

Hedgehog pathway gene expression during early development of the molar tooth root in the mouse.

Sonic hedgehog is a secreted protein important for many aspects of embryonic development. In the developing tooth, Shh expression is restricted to the epithelial compartment and plays an important role during both initiation and subsequent coronal morphogenesis. We have investigated the expression of Shh and constituent members of the signalling pathway during early development of the molar tooth root in the mouse and find the presence of transcripts in Hertwig's epithelial root sheath.

Tbx1 is expressed at multiple sites of epithelial-mesenchymal interaction during early development of the facial complex.

TBX1 encodes a T-box-containing transcription factor, which is thought to be a key player in the aetiology of the DiGeorge and Velocardiofacial syndromes (DGS/VCFS). In addition to defects affecting structures derived from the pharyngeal pouches, these patients exhibit varying degrees of facial dysmorphology and cleft palate. We have analysed the expression of murine Tbx1 during early facial development and found transcripts at sites of known epithelial-mesenchymal interaction.