期刊
REPRODUCTIVE TOXICOLOGY
卷 99, 期 -, 页码 109-130出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2020.10.014
关键词
Retinoid signaling; Developmental toxicity; Skeletal development
资金
- Chemical Safety for Sustainability (CSS) National Research Program, Virtual Tissue Models (CSS 5.3) project of the U.S. Environmental Protection Agency
ATRA, the active form of vitamin A, plays a crucial role in regulating the patterning and specification of vertebrate embryos. Adverse developmental phenotypes can occur in various animal models due to experimental retinoid depletion or excess during pregnancy. ATRA signaling often involves mutual antagonism with FGF signaling, and errors or disruptions in retinoid signaling can lead to severe deficiencies in skeletal development.
All-trans retinoic acid (ATRA), the biologically active form of vitamin A, is instrumental in regulating the patterning and specification of the vertebrate embryo. Various animal models demonstrate adverse developmental phenotypes following experimental retinoid depletion or excess during pregnancy. Windows of vulnerability for altered skeletal patterning coincide with early specification of the body plan (gastrulation) and regional specification of precursor cell populations forming the facial skeleton (cranial neural crest), vertebral column (somites), and limbs (lateral plate mesoderm) during organogenesis. A common theme in physiological roles of ATRA signaling is mutual antagonism with FGF signaling. Consequences of genetic errors or environmental disruption of retinoid signaling include stage- and region-specific homeotic transformations to severe deficiencies for various skeletal elements. This review derives from an annex in Detailed Review Paper (DRP) of the OECD Test Guidelines Programme (Project 4.97) to support recommendations regarding assay development for the retinoid system and the use of resulting data in a regulatory context for developmental and reproductive toxicity (DART) testing.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据