The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform
Christoph Viebahn - One of the best experts on this subject based on the ideXlab platform.
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pitx2 and nodal as conserved early markers of the anterior posterior axis in the Rabbit Embryo
Annals of Anatomy-anatomischer Anzeiger, 2018Co-Authors: Ruben Ploger, Christoph ViebahnAbstract:Abstract Attaining molecular and morphological axial polarity during gastrulation is a fundamental early requirement for normal development of the Embryo. In mammals, the first morphological sign of the anterior–posterior axis appears anteriorly in the form of the anterior marginal crescent (or anterior visceral endoderm) while in the avian the first such sign is the Koller’s sickle at the posterior pole of the Embryonic disc. Despite this inverse mode of axis formation many genes and molecular pathways involved in various steps of this process seem to be evolutionarily conserved amongst amniotes, the nodal gene being a well-known example with its functional involvement prior and during gastrulation. The pitx2 gene, however, is a new candidate described in the chick as an early marker for anterior–posterior polarity and as a regulator of axis formation including twinning. To find out whether pitx2 has retained its inductive and early marker function during the evolution of mammals this study analyses pitx2 and nodal expression at parallel stages during formation of the anterior–posterior polarity in the early Rabbit Embryo using whole-mount in situ hybridization and serial light-microscopical sections. At a late pre-gastrulation stage a localized reduction of nodal expression presages the position of the anterior pole of the Embryonic disc and thus serves as the earliest molecular marker of anterior–posterior polarity known so far. Pitx2 is expressed in a polarized manner in the anterior marginal crescent and in the posterior half of the Embryonic disc during further development. In the anterior segment of the posterior pitx2 expression domain, the anterior streak domain (ASD) is defined by nodal expression as a hypothetical progenitor region of the anterior half of the primitive streak. The expression patterns of both genes thus serve as signs of a conserved involvement in early axis formation in amniotes and, possibly, in twinning in mammals as well.
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rho kinase activity controls directional cell movements during primitive streak formation in the Rabbit Embryo
Development, 2015Co-Authors: Viktoria Stankova, Nikoloz Tsikolia, Christoph ViebahnAbstract:During animal gastrulation, the specification of the Embryonic axes is accompanied by epithelio-mesenchymal transition (EMT), the first major change in cell shape after fertilization. EMT takes place in disparate topographical arrangements, such as the circular blastopore of amphibians, the straight primitive streak of birds and mammals or in intermediate gastrulation forms of other amniotes such as reptiles. Planar cell movements are prime candidates to arrange specific modes of gastrulation but there is no consensus view on their role in different vertebrate classes. Here, we test the impact of interfering with Rho kinase-mediated cell movements on gastrulation topography in blastocysts of the Rabbit, which has a flat Embryonic disc typical for most mammals. Time-lapse video microscopy, electron microscopy, gene expression and morphometric analyses of the effect of inhibiting ROCK activity showed – besides normal specification of the organizer region – a dose-dependent disruption of primitive streak formation; this disruption resulted in circular, arc-shaped or intermediate forms, reminiscent of those found in amphibians, fishes and reptiles. Our results reveal a crucial role of ROCK-controlled directional cell movements during Rabbit primitive streak formation and highlight the possibility that temporal and spatial modulation of cell movements were instrumental for the evolution of gastrulation forms.
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Hypoblast controls mesoderm generation and axial patterning in the gastrulating Rabbit Embryo
Development Genes and Evolution, 2004Co-Authors: Jan Idkowiak, Gunnar Weisheit, Juliane Plitzner, Christoph ViebahnAbstract:Gastrulation in higher vertebrate species classically commences with the generation of mesoderm cells in the primitive streak by epithelio-mesenchymal transformation of epiblast cells. However, the primitive streak also marks, with its longitudinal orientation in the posterior part of the conceptus, the anterior-posterior (or head-tail) axis of the Embryo. Results obtained in chick and mouse suggest that signals secreted by the hypoblast (or visceral endoderm), the extraEmbryonic tissue covering the epiblast ventrally, antagonise the mesoderm induction cascade in the anterior part of the epiblast and thereby restrict streak development to the posterior pole (and possibly initiate head development anteriorly). In this paper we took advantage of the disc-shape morphology of the Rabbit gastrula for defining the expression compartments of the signalling molecules Cerberus and Dickkopf at pre-gastrulation and early gastrulation stages in a mammal other than the mouse. The two molecules are expressed in novel expression compartments in a complementary fashion both in the hypoblast and in the emerging primitive streak. In loss-of-function experiments, carried out in a New-type culturing system, hypoblast was removed prior to culture at defined stages before and at the beginning of gastrulation. The epiblast shows a stage-dependent and topographically restricted susceptibility to express Brachyury , a T-box gene pivotal for mesoderm formation, and to transform into (histologically proven) mesoderm. These results confirm for the mammalian Embryo that the anterior-posterior axis of the conceptus is formed first as a molecular prepattern in the hypoblast and then irrevocably fixed, under the control of signals secreted from the hypoblast, by epithelio-mesenchymal transformation (primitive streak formation) in the epiblast.
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polarity in the Rabbit Embryo
Seminars in Cell & Developmental Biology, 2004Co-Authors: Jan Idkowiak, Gunnar Weisheit, Christoph ViebahnAbstract:The main aim of the gastrulation process is commonly regarded to be the generation of the definitive germ layers known as mesoderm, endoderm and ectoderm. Here we discuss how the topography of gene expression, cellular migration and proliferative activity in the preliminary germ layers (hypoblast and epiblast) of the Rabbit Embryo reveal the sequence of events that establishes the three major body axes. We present a testable model in which a combination of cellular movement in the hypoblast with a morphogen gradient created by the (extraEmbryonic) trophoblast creates morphological polarity in the Embryo and, hence, the co-ordinates for germ layer formation.
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low proliferative and high migratory activity in the area of brachyury expressing mesoderm progenitor cells in the gastrulating Rabbit Embryo
Development, 2002Co-Authors: Christoph Viebahn, Christof Stortz, Sally A Mitchell, Martin BlumAbstract:General mechanisms initiating the gastrulation process in early animal development are still elusive, not least because Embryonic morphology differs widely among species. The Rabbit Embryo is revived here as a model to study vertebrate gastrulation, because its relatively simple morphology at the appropriate stages makes interspecific differences and similarities particularly obvious between mammals and birds. Three approaches that centre on mesoderm specification as a key event at the start of gastrulation were chosen. (1) A cDNA fragment encoding 212 amino acids of the Rabbit Brachyury gene was cloned by RT-PCR and used as a molecular marker for mesoderm progenitors. Whole-mount in situ hybridisation revealed single Brachyury -expressing cells in the epiblast at 6.2 days post conception, i.e. several hours before the first ingressing mesoderm cells can be detected histologically. With the anterior marginal crescent as a landmark, these mesoderm progenitors are shown to lie in a posterior quadrant of the Embryonic disc, which we call the posterior gastrula extension (PGE), for reasons established during the following functional analysis. (2) Vital dye (DiI) labelling in vitro suggests that epiblast cells arrive in the PGE from anterior parts of the Embryonic disc and then move within this area in a complex pattern of posterior, centripetal and anterior directions to form the primitive streak. (3) BrdU labelling shows that proliferation is reduced in the PGE, while the remaining anterior part of the Embryonic disc contains several areas of increased proliferation. These results reveal similarities with the chick with respect to Brachyury expression and cellular migration. They differ, however, in that local differences in proliferation are not seen in the pre-streak avian Embryo. Rather, Rabbit epiblast cells start mesoderm differentiation in a way similar to Drosophila , where a transient downregulation of proliferation initiates mesoderm differentiation and, hence, gastrulation.
Bruce K Beyer - One of the best experts on this subject based on the ideXlab platform.
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comparing rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on systemic dose and developmental effects
Critical Reviews in Toxicology, 2017Co-Authors: Peter T Theunissen, Sonia Beken, Bruce K Beyer, William J Breslin, Gregg D Cappon, Connie L Chen, Gary W Chmielewski, Luc De Schaepdrijver, Brian P Enright, Jennifer E ForemanAbstract:A database of Embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and Rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and Rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the Rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the Rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and Rabbit were equally sensitive. The relative extent of Embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and Rabbit studies. Individual rat and Rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of Embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and Rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.
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comparison of rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on the nature and severity of developmental effects
Critical Reviews in Toxicology, 2016Co-Authors: Sonia Beken, Peter T Theunissen, Bruce K BeyerAbstract:AbstractRegulatory non-clinical safety testing of human pharmaceuticals typically requires Embryo–fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and Rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or Rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of Rabbit studies identifying an EFDT signal. For...
Peter T Theunissen - One of the best experts on this subject based on the ideXlab platform.
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comparing rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on systemic dose and developmental effects
Critical Reviews in Toxicology, 2017Co-Authors: Peter T Theunissen, Sonia Beken, Bruce K Beyer, William J Breslin, Gregg D Cappon, Connie L Chen, Gary W Chmielewski, Luc De Schaepdrijver, Brian P Enright, Jennifer E ForemanAbstract:A database of Embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and Rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and Rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the Rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the Rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and Rabbit were equally sensitive. The relative extent of Embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and Rabbit studies. Individual rat and Rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of Embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and Rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.
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comparison of rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on the nature and severity of developmental effects
Critical Reviews in Toxicology, 2016Co-Authors: Sonia Beken, Peter T Theunissen, Bruce K BeyerAbstract:AbstractRegulatory non-clinical safety testing of human pharmaceuticals typically requires Embryo–fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and Rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or Rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of Rabbit studies identifying an EFDT signal. For...
Sonia Beken - One of the best experts on this subject based on the ideXlab platform.
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comparing rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on systemic dose and developmental effects
Critical Reviews in Toxicology, 2017Co-Authors: Peter T Theunissen, Sonia Beken, Bruce K Beyer, William J Breslin, Gregg D Cappon, Connie L Chen, Gary W Chmielewski, Luc De Schaepdrijver, Brian P Enright, Jennifer E ForemanAbstract:A database of Embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and Rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and Rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the Rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the Rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and Rabbit were equally sensitive. The relative extent of Embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and Rabbit studies. Individual rat and Rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of Embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and Rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.
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comparison of rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on the nature and severity of developmental effects
Critical Reviews in Toxicology, 2016Co-Authors: Sonia Beken, Peter T Theunissen, Bruce K BeyerAbstract:AbstractRegulatory non-clinical safety testing of human pharmaceuticals typically requires Embryo–fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and Rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or Rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of Rabbit studies identifying an EFDT signal. For...
Jennifer E Foreman - One of the best experts on this subject based on the ideXlab platform.
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comparing rat and Rabbit Embryo fetal developmental toxicity data for 379 pharmaceuticals on systemic dose and developmental effects
Critical Reviews in Toxicology, 2017Co-Authors: Peter T Theunissen, Sonia Beken, Bruce K Beyer, William J Breslin, Gregg D Cappon, Connie L Chen, Gary W Chmielewski, Luc De Schaepdrijver, Brian P Enright, Jennifer E ForemanAbstract:A database of Embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and Rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and Rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the Rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the Rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and Rabbit were equally sensitive. The relative extent of Embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and Rabbit studies. Individual rat and Rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of Embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and Rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.
