Maria Zoupa - Academia.edu (original) (raw)

Papers by Maria Zoupa

Research paper thumbnail of Additional file 3: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

KEGG pathway analysis. (XLSX 11Â kb)

Research paper thumbnail of Additional file 2: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

List of genes differentially expressed in WT compared to heterozygous palates (nâ =â 400) (Group ... more List of genes differentially expressed in WT compared to heterozygous palates (nâ =â 400) (Group B). (XLSX 33Â kb)

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

The International Journal of Developmental Biology, 2006

TBX1 encodes a T-box-containing transcription factor, which is thought to be a key player in the ... more 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 epithelialmesenchymal interaction. In particular, Tbx1 was expressed in epithelium of the early facial processes, including the fronto-nasal, medial and lateral nasal and palatine. Transcripts were also localised to the epithelium of developing tooth germs and hair follicles at several stages during their early development. Together, these expression domains suggest a role for Tbx1 in mediating epithelial-mesenchymal signalling in regions of the developing face, a finding which is consistent with the spectrum of facial deformity encountered amongst subjects affected by DGS/VCFS.

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

Gene Expression Patterns, 2007

Scube genes encode a small group of secreted plasma membrane-associated proteins characterised by... more 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. However, as development progressed, strong expression was detected in ectodermal, endodermal and mesodermal tissues. In particular, the neural tube, branchial arches and fronto-nasal region, the dermomyotome of diVerentiating somites and the limb buds. Scube3 also demonstrated a highly restricted and speciWc expression domain in the developing tooth and hair follicle. At later stages, expression was also localised to cartilaginous primordia of the skeleton and regions of intramembranous bone formation in the developing craniofacial region. In addition, Scube3 transcripts were also found in the developing kidney.

Research paper thumbnail of Hedgehog pathway gene expression during early development of the molar tooth root in the mouse

Gene Expression Patterns, 2007

Sonic hedgehog is a secreted protein important for many aspects of embryonic development. In the ... more 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 Wnd the presence of transcripts in Hertwig's epithelial root sheath. These epithelial cells of the root sheath and the surrounding apical mesenchyme of the dental papilla and follicle also expressed the Shh receptor Ptc1, agonist Smo and Gli downstream transcriptional eVectors; however, this response occurred over short range. In contrast, the Shh antagonists Hip1 and Gas1 were both expressed at a distance from these responding cells, in more peripheral regions of the developing root. Transcripts of the Skn acyl transferase lacked speciWc expression in early root structures.

Research paper thumbnail of The role of TBX1 in the developing secondary palate

British Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of Additional file 4: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

Quantitative RT-PCR primer/probe list. This table contains a complete list of the 63 primers/ pro... more Quantitative RT-PCR primer/probe list. This table contains a complete list of the 63 primers/ probes used in the real-time quantitative RT-PCR analysis of gene expression in the developing palate of Tbx1 mice. (DOCX 90Â kb)

Research paper thumbnail of Additional file 1: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

Tbx1 lacZ reporter expression in the developing murine palate. (A) E12.5; (B) E13.5; (C) E14.5; (... more Tbx1 lacZ reporter expression in the developing murine palate. (A) E12.5; (B) E13.5; (C) E14.5; (D) E15.5. Tbx1 is expressed in epithelium of the primary (yellow arrowhead) and secondary palate (white arrowhead) with expression persisting in these regions during the process of fusion (orange and pink arrowheads, respectively). Expression is also seen in the maxillary incisor tooth germs (green arrowhead), maxillary molar tooth germs (red arrowhead) and palatal rugae (black arrows). (TIF 2146Â kb)

Research paper thumbnail of Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos

Food and Chemical Toxicology

A challenge in cumulative risk assessment is to model hazard of mixtures. EFSA proposed to only c... more 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. We combined chemicals with similar mode of action (MOA), i.e. the triazoles cyproconazole, triadimefon and flusilazole; next, reference compounds cyproconazole or triadimefon were combined with dissimilar acting compounds, TCDD, thiram, VPA, prochloraz, fenpropimorph, PFOS, or endosulfan. These mixtures were designed as (near) equipotent combinations of the contributing compounds, in a range of cumulative concentrations. Dose-addition was assessed by evaluation of the overlap of responses of each of the 14 tested binary mixtures with those of the single compounds. All 10 test compounds induced an increase of the M-PQ angle, with varying potency and specificity. Mixture responses as predicted by dose-addition did not deviate from the observed responses, supporting dose-addition as a valid assumption for mixture risk assessment. Importantly, dose-addition was found irrespective of MOA of contributing chemicals.

Research paper thumbnail of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

BMC genomics, Jan 4, 2018

Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, includi... more 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. However, less is known about its role during palatogenesis. To assess the influence of Tbx1 function on gene expression profile within the developing palate we performed a microarray screen using total RNA isolated from the secondary palate of E13.5 mouse embryos wild type, heterozygous and mutant for Tbx1. Expression-level filtering and statistical analysis revealed a total of 577 genes differentially expressed across genotypes. Data were clustered into 3 groups based on comparison between genotypes. Group A was comp...

Research paper thumbnail of Zebrafish as an Alternative Vertebrate Model for Investigating Developmental Toxicity—The Triadimefon Example

International Journal of Molecular Sciences

Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in se... more 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. Our analysis revealed significant developmental defects at the highest tested concentration including somite deformities, severe craniofacial defects, a cleft phenotype along the three primary neural divisions, a rigorously hypoplastic or even absent mandible and a hypoplastic morphology of the pharyngeal arches. Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia and inhibited or absent blood circulation were also observed. Our results revealed that the presented zebrafish phenotypes are comparable to those seen in other organism models and those derived from human observations as a result of triadimefon exposure. We therefore demonstrated that zebrafish provide an excellent system for study of compounds with toxic significance and can be used as an alternative model for developmental toxicity studies to predict effects in mammals.

Research paper thumbnail of Tooth development: 2. Regenerating teeth in the laboratory

Dental update

Tooth loss can occur for a number of reasons and a variety of prosthetic tooth replacement soluti... more 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.

Research paper thumbnail of Tooth development: 1. Generating teeth in the embryo

Dental update, 2006

Teeth are organs that develop in the embryo via a series of interactions between oral epithelium ... more 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.

Research paper thumbnail of Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

Developmental Biology, 2009

Research paper thumbnail of Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

Developmental Biology, 2009

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

International Journal of Developmental Biology, 2006

TBX1 encodes a T-box-containing transcription factor, which is thought to be a key player in the ... more 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 epithelialmesenchymal interaction. In particular, Tbx1 was expressed in epithelium of the early facial processes, including the fronto-nasal, medial and lateral nasal and palatine. Transcripts were also localised to the epithelium of developing tooth germs and hair follicles at several stages during their early development. Together, these expression domains suggest a role for Tbx1 in mediating epithelial-mesenchymal signalling in regions of the developing face, a finding which is consistent with the spectrum of facial deformity encountered amongst subjects affected by DGS/VCFS.

Research paper thumbnail of Additional file 3: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

KEGG pathway analysis. (XLSX 11Â kb)

Research paper thumbnail of Additional file 2: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

List of genes differentially expressed in WT compared to heterozygous palates (nâ =â 400) (Group ... more List of genes differentially expressed in WT compared to heterozygous palates (nâ =â 400) (Group B). (XLSX 33Â kb)

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

The International Journal of Developmental Biology, 2006

TBX1 encodes a T-box-containing transcription factor, which is thought to be a key player in the ... more 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 epithelialmesenchymal interaction. In particular, Tbx1 was expressed in epithelium of the early facial processes, including the fronto-nasal, medial and lateral nasal and palatine. Transcripts were also localised to the epithelium of developing tooth germs and hair follicles at several stages during their early development. Together, these expression domains suggest a role for Tbx1 in mediating epithelial-mesenchymal signalling in regions of the developing face, a finding which is consistent with the spectrum of facial deformity encountered amongst subjects affected by DGS/VCFS.

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

Gene Expression Patterns, 2007

Scube genes encode a small group of secreted plasma membrane-associated proteins characterised by... more 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. However, as development progressed, strong expression was detected in ectodermal, endodermal and mesodermal tissues. In particular, the neural tube, branchial arches and fronto-nasal region, the dermomyotome of diVerentiating somites and the limb buds. Scube3 also demonstrated a highly restricted and speciWc expression domain in the developing tooth and hair follicle. At later stages, expression was also localised to cartilaginous primordia of the skeleton and regions of intramembranous bone formation in the developing craniofacial region. In addition, Scube3 transcripts were also found in the developing kidney.

Research paper thumbnail of Hedgehog pathway gene expression during early development of the molar tooth root in the mouse

Gene Expression Patterns, 2007

Sonic hedgehog is a secreted protein important for many aspects of embryonic development. In the ... more 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 Wnd the presence of transcripts in Hertwig's epithelial root sheath. These epithelial cells of the root sheath and the surrounding apical mesenchyme of the dental papilla and follicle also expressed the Shh receptor Ptc1, agonist Smo and Gli downstream transcriptional eVectors; however, this response occurred over short range. In contrast, the Shh antagonists Hip1 and Gas1 were both expressed at a distance from these responding cells, in more peripheral regions of the developing root. Transcripts of the Skn acyl transferase lacked speciWc expression in early root structures.

Research paper thumbnail of The role of TBX1 in the developing secondary palate

British Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of Additional file 4: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

Quantitative RT-PCR primer/probe list. This table contains a complete list of the 63 primers/ pro... more Quantitative RT-PCR primer/probe list. This table contains a complete list of the 63 primers/ probes used in the real-time quantitative RT-PCR analysis of gene expression in the developing palate of Tbx1 mice. (DOCX 90Â kb)

Research paper thumbnail of Additional file 1: of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

Tbx1 lacZ reporter expression in the developing murine palate. (A) E12.5; (B) E13.5; (C) E14.5; (... more Tbx1 lacZ reporter expression in the developing murine palate. (A) E12.5; (B) E13.5; (C) E14.5; (D) E15.5. Tbx1 is expressed in epithelium of the primary (yellow arrowhead) and secondary palate (white arrowhead) with expression persisting in these regions during the process of fusion (orange and pink arrowheads, respectively). Expression is also seen in the maxillary incisor tooth germs (green arrowhead), maxillary molar tooth germs (red arrowhead) and palatal rugae (black arrows). (TIF 2146Â kb)

Research paper thumbnail of Dose addition in chemical mixtures inducing craniofacial malformations in zebrafish (Danio rerio) embryos

Food and Chemical Toxicology

A challenge in cumulative risk assessment is to model hazard of mixtures. EFSA proposed to only c... more 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. We combined chemicals with similar mode of action (MOA), i.e. the triazoles cyproconazole, triadimefon and flusilazole; next, reference compounds cyproconazole or triadimefon were combined with dissimilar acting compounds, TCDD, thiram, VPA, prochloraz, fenpropimorph, PFOS, or endosulfan. These mixtures were designed as (near) equipotent combinations of the contributing compounds, in a range of cumulative concentrations. Dose-addition was assessed by evaluation of the overlap of responses of each of the 14 tested binary mixtures with those of the single compounds. All 10 test compounds induced an increase of the M-PQ angle, with varying potency and specificity. Mixture responses as predicted by dose-addition did not deviate from the observed responses, supporting dose-addition as a valid assumption for mixture risk assessment. Importantly, dose-addition was found irrespective of MOA of contributing chemicals.

Research paper thumbnail of Gene expression profiling in the developing secondary palate in the absence of Tbx1 function

BMC genomics, Jan 4, 2018

Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, includi... more 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. However, less is known about its role during palatogenesis. To assess the influence of Tbx1 function on gene expression profile within the developing palate we performed a microarray screen using total RNA isolated from the secondary palate of E13.5 mouse embryos wild type, heterozygous and mutant for Tbx1. Expression-level filtering and statistical analysis revealed a total of 577 genes differentially expressed across genotypes. Data were clustered into 3 groups based on comparison between genotypes. Group A was comp...

Research paper thumbnail of Zebrafish as an Alternative Vertebrate Model for Investigating Developmental Toxicity—The Triadimefon Example

International Journal of Molecular Sciences

Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in se... more 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. Our analysis revealed significant developmental defects at the highest tested concentration including somite deformities, severe craniofacial defects, a cleft phenotype along the three primary neural divisions, a rigorously hypoplastic or even absent mandible and a hypoplastic morphology of the pharyngeal arches. Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia and inhibited or absent blood circulation were also observed. Our results revealed that the presented zebrafish phenotypes are comparable to those seen in other organism models and those derived from human observations as a result of triadimefon exposure. We therefore demonstrated that zebrafish provide an excellent system for study of compounds with toxic significance and can be used as an alternative model for developmental toxicity studies to predict effects in mammals.

Research paper thumbnail of Tooth development: 2. Regenerating teeth in the laboratory

Dental update

Tooth loss can occur for a number of reasons and a variety of prosthetic tooth replacement soluti... more 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.

Research paper thumbnail of Tooth development: 1. Generating teeth in the embryo

Dental update, 2006

Teeth are organs that develop in the embryo via a series of interactions between oral epithelium ... more 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.

Research paper thumbnail of Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

Developmental Biology, 2009

Research paper thumbnail of Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

Developmental Biology, 2009

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

International Journal of Developmental Biology, 2006

TBX1 encodes a T-box-containing transcription factor, which is thought to be a key player in the ... more 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 epithelialmesenchymal interaction. In particular, Tbx1 was expressed in epithelium of the early facial processes, including the fronto-nasal, medial and lateral nasal and palatine. Transcripts were also localised to the epithelium of developing tooth germs and hair follicles at several stages during their early development. Together, these expression domains suggest a role for Tbx1 in mediating epithelial-mesenchymal signalling in regions of the developing face, a finding which is consistent with the spectrum of facial deformity encountered amongst subjects affected by DGS/VCFS.