Related Experiment Video
Updated: May 16, 2025
Application of Impermeable Barriers Combined with Candidate Factor Soaked Beads to Study Inductive Signals in the Chick
Published on: November 17, 2016
Perillic acid disrupts the specification of germ layers by upregulating the FGF/MAPK pathway
Gang-Ho Yoon1, Dong-Seok Park1,2, Myeoung Su Kim1
1Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Korea.
Background:
Xenopus embryo is an ideal model for teratogenesis assays to assess the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis.
Objective:
In our screening of a chemical library with frog embryo to identify novel compounds that exert specific effects on key cellular signaling pathways, perillic acid (PA) was found to disrupt germ layer specification in early development. Thus, the mechanism underlying this effect was investigated.
Methods:
Embryos were exposed to PA during a specific period of early development to observe stage-specific morphological alterations induced by this compound. Whole-mount in situ hybridization was performed to examine its effects on ectodermal and mesodermal differentiation and the anterior-posterior patterning of neural tissue. Western blotting analysis was employed to identify the signaling pathways through which PA influences germ layer formation in Xenopus development.
Results:
PA-treated embryos exhibited the shortening of the anterior-posterior body axis, truncation of craniofacial structures and malformation of neural crest (NC). These severe morphological defects occurred when embryos became exposed to PA during the gastrula stages. Consistent with these phenotypes, treatment with PA caused significant expansion of neural tissue concomitant with a reduction of epidermal and NC cell fates. Furthermore, PA induced the caudalization of neural fate and expressions of paraxial mesodermal genes, recapitulating the activity of the FGF/MAPK signals in germ layer specification. In line with this, ERK activation could be induced by PA treatment, which was mediated by the FGFR1 pathway.
Conclusion:
PA affects the anterior-posterior neural patterning and mesodermal specification by activating the FGF/MAPK signaling pathway.
Insights
Perillic acid (PA) disrupts early frog development by affecting germ layer specification. This compound activates FGF/MAPK signaling, leading to neural patterning defects and altered mesodermal development.
Area of Science:
- Developmental Biology
- Teratology
- Molecular Signaling
Background:
- The Xenopus embryo serves as a vital model for teratogenesis assays, evaluating compound effects on early development and tissue homeostasis.
- Screening a chemical library using frog embryos identified perillic acid (PA) as a disruptor of germ layer specification.
Purpose of the Study:
- Investigate the mechanism by which perillic acid (PA) disrupts germ layer specification in early Xenopus development.
- Identify the specific cellular signaling pathways affected by PA exposure.
Main Methods:
- Exposing Xenopus embryos to PA during specific developmental stages to observe morphological alterations.
- Utilizing whole-mount in situ hybridization to assess differentiation of ectodermal and mesodermal tissues, and neural patterning.
- Employing Western blotting to analyze signaling pathway activation, specifically focusing on FGF/MAPK signaling.
Main Results:
- PA exposure during gastrulation induced anterior-posterior axis shortening, craniofacial truncation, and neural crest (NC) malformations.
- PA treatment led to expanded neural tissue at the expense of epidermal and NC cell fates.
- PA activated FGF/MAPK signaling, evidenced by ERK activation via the FGFR1 pathway, and induced caudalization of neural and mesodermal fates.
Conclusions:
- Perillic acid (PA) significantly impacts anterior-posterior neural patterning and mesodermal specification in Xenopus embryos.
- The observed developmental defects are mediated through the activation of the FGF/MAPK signaling pathway by PA.
More Related Videos
Related Concept Videos
01:07MAPK Signaling Cascades
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:33Hedgehog Signaling Pathway