RRC ID 70575
Author Nishiya N, Yonezawa H.
Title Domestication of chemicals attacking metazoan embryogenesis: identification of safe natural products modifying developmental signaling pathways in human.
Journal J Antibiot (Tokyo)
Abstract Soil microorganisms are rich sources of bioactive natural products. Interspecies interactions are the cues of their production and refine biological activities. These interactions in natural environments include the interplay between microorganisms and Metazoans (animals), such as nematodes, insects, and ticks. Chemical intercellular communication modulators could exert ideal Metazoan-selective toxicity for defending microorganisms. Developmental signaling pathways, such as the Notch, TGF-beta, and Wnt pathways, are intercellular communication networks that contribute to the reproducible formation of complex higher-order Metazoan body structures. Natural modifiers of the developmental signaling pathway are attractive therapeutic seeds for carcinoma and sarcoma treatment. However, these fundamental signaling pathways also play indispensable physiological roles and their perturbation could lead to toxicity, such as defects in stem cell physiology and tissue regeneration processes. In this review, we introduce a screening system that selects developmental signaling inhibitors with wide therapeutic windows using zebrafish embryonic phenotypes and provide examples of microorganism-derived Wnt pathway inhibitors. Moreover, we discuss safety prospects of the developmental signaling inhibitors.
Volume 74(10)
Pages 651-659
Published 2021-10-1
DOI 10.1038/s41429-021-00461-y
PII 10.1038/s41429-021-00461-y
PMID 34381189
MeSH Animals Biological Products / pharmacology* Biological Products / toxicity* Embryonic Development / drug effects* Gene Expression Regulation, Developmental / drug effects Humans Soil Microbiology
IF 2.668
Zebrafish RIKEN WT