FETAX Assay for Evaluation of Developmental Toxicity

Mouche, Isabelle; Malesic, Laure; Gillardeaux, O.

doi:10.1007/978-1-60761-849-2_15

Cited by 38 publications

(16 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Anatomical development of frog tadpoles has been described quantitatively in ecological and toxicological contexts (Mouche et al, ; Lima and Pederassi, ). While quantitative analyses of later stage Xenopus tadpoles and metamorphs is more common (Rose, ; Asquith and Vonesh, ; Vandenberg et al, ), there are no quantitative descriptions of the craniofacial anatomy during early development.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Orofacial Development and Median Clefts in Xenopus Laevis

Kennedy

Dickinson

2014

The Anatomical Record

View full text Add to dashboard Cite

Xenopus has become a useful tool to study the molecular mechanisms underlying orofacial development. However, few quantitative analyses exist to describe the anatomy of this region. In this study we combine traditional facial measurements with geometric morphometrics to describe anatomical changes in the orofacial region during normal and abnormal development. Facial measurements and principal component (PC) analysis indicate that during early tadpole development the face expands primarily in the midface region accounting for the development of the upper jaw and primary palate. The mouth opening correspondingly becomes flatter and wider as it incorporates the jaw elements. A canonical variate analysis of orofacial and mouth opening shape emphasized that changes in the orofacial shape occur gradually. Orofacial anatomy was quantified after altered levels of retinoic acid using all-trans retinoic acid or an inhibitor of retinoic acid receptors or by injecting antisense oligos targeting RALDH2. Such perturbations resulted in major decreases in the width of the midface and the mouth opening illustrated in facial measurements and a PC analysis. The mouth opening shape also had a gap in the primary palate resulting in a median cleft in the mouth opening that was only illustrated quantitatively in the morphometric analysis. Finally, canonical and discriminant function analysis statistically distinguished the orofacial and mouth opening shape changes among the different modes used to alter retinoic acid signaling levels. By combining quantitative analyses with molecular studies of orofacial development we will be better equipped to understand the complex morphogenetic processes involved in palate development and clefting. Anat Rec, 297:834-855, 2014. V C 2014 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Orofacial Development and Median Clefts in Xenopus Laevis

Kennedy

Dickinson

2014

The Anatomical Record

View full text Add to dashboard Cite

show abstract

“…; Mouche et al. ; Leconte & Mouche, ). This preliminary screen represents the first tier of an inverse drug screen, of the variety described by (Adams & Levin, ), in which drugs are tested in a hierarchical manner according to target specificity, to rapidly bypass large families with no apparent roles and progressively home in on targets with interesting functions.…”

Section: Introductionmentioning

confidence: 96%

Neurotransmitter signaling pathways required for normal development inXenopus laevisembryos: a pharmacological survey screen

Sullivan

Levin

2016

Journal of Anatomy

View full text Add to dashboard Cite

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, we report results from a loss- and gain-of-function survey, using pharmacologic modulators of several neurotransmitter pathways to examine possible roles in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic, and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations including craniofacial defects, hyperpigmentation, muscle mispatterning, and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy.

show abstract

“…To further examine the teratogenic potential of PTU and MMI, we investigated potential teratogenicity during embryogenesis of the frog Xenopus tropicalis. The frog embryo is an excellent model for teratogenic studies, since embryos can be treated, independent of maternal effects, and studies can be performed at very early stages of development that are difficult to examine in mammals (20). As a tetrapod, much of the basic biology that establishes the body axis and organ primordia are conserved among mammals and frogs, as well (21).…”

mentioning

confidence: 99%

Embryonic exposure to propylthiouracil disrupts left‐right patterning inXenopusembryos

Veenendaal¹,

Ulmer

Boskovski³

et al. 2012

FASEB j.

View full text Add to dashboard Cite

Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy.

show abstract

FETAX Assay for Evaluation of Developmental Toxicity

Cited by 38 publications

References 6 publications

Quantitative Analysis of Orofacial Development and Median Clefts in Xenopus Laevis

Quantitative Analysis of Orofacial Development and Median Clefts in Xenopus Laevis

Neurotransmitter signaling pathways required for normal development inXenopus laevisembryos: a pharmacological survey screen

Embryonic exposure to propylthiouracil disrupts left‐right patterning inXenopusembryos

Contact Info

Product

Resources

About