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Caffeic acid phenethyl ester disrupts germ layer specification in Xenopus embryos
Gang-Ho Yoon1, Myeoung Su Kim1, Sun-Cheol Choi1
1Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
Abstract:
Xenopus embryo serves as an ideal model for teratogenesis assays to observe the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening of a chemical library with frog embryo, caffeic acid phenethyl ester (CAPE) was found to upregulate the FGF/MAPK pathway, disrupting germ layer formation in early development. Exposure to CAPE interfered with the formation of anterior-posterior body axis and of ectodermal derivatives such as eyes, dorsal fin and pigment cells. These inhibitory effects were achieved by promoting paraxial mesodermal specification and neural differentiation concomitant with a repression of epidermal and neural crest cell fates. This compound also induced the caudalization of anterior neural fate, thereby recapitulating the activity of the FGF/MAPK signals in the anterior-posterior patterning of neural tissue. Consistently, phosphorylation of extracellular signal-regulated kinase (ERK) was elevated in CAPE-treated cells, which was mediated by the FGFR1 and FGFR4 pathway. Together, these results suggest that CAPE functions as an activator of the FGF/MAPK signaling pathway, generating severe teratogenic effects on germ layer specification in vertebrate early development.
Insights
Caffeic acid phenethyl ester (CAPE) disrupts early vertebrate development by activating the FGF/MAPK pathway. This teratogenic effect impacts germ layer formation, body axis patterning, and cell fate specification in Xenopus embryos.
Area of Science:
- Developmental Biology
- Teratology
- Molecular Signaling
Background:
- Xenopus embryos are valuable models for teratogenesis assays.
- Understanding compound effects on early development and tissue homeostasis is crucial.
Purpose of the Study:
- To investigate the teratogenic effects of caffeic acid phenethyl ester (CAPE) in Xenopus embryos.
- To elucidate the molecular mechanisms underlying CAPE-induced developmental disruptions.
Main Methods:
- Screening of a chemical library using frog embryos.
- Analysis of germ layer formation, body axis patterning, and cell differentiation.
- Assessment of FGF/MAPK pathway activation, including ERK phosphorylation and FGFR1/FGFR4 involvement.
Main Results:
- CAPE upregulates the FGF/MAPK pathway, leading to disrupted germ layer formation.
- Exposure to CAPE interferes with anterior-posterior body axis and ectodermal derivative development.
- CAPE promotes paraxial mesoderm and neural differentiation while repressing epidermal and neural crest fates, causing anterior neural fate caudalization.
Conclusions:
- CAPE acts as an activator of the FGF/MAPK signaling pathway.
- CAPE induces severe teratogenic effects on germ layer specification in vertebrate early development.
- The findings highlight the critical role of FGF/MAPK signaling in embryonic patterning and cell fate determination.
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