XB-ART-53008Genesis January 1, 2017; 55 (1-2):
Frogs model man: In vivo thyroid hormone signaling during development.
Thyroid hormone (TH) signaling comprises TH transport across cell membranes, metabolism by deiodinases, and molecular mechanisms of gene regulation. Proper TH signaling is essential for normal perinatal development, most notably for neurogenesis and fetal growth. Knowledge of perinatal TH endocrinology needs improvement to provide better treatments for premature infants and endocrine diseases during gestation and to counteract effects of endocrine disrupting chemicals. Studies in amphibians have provided major insights to understand in vivo mechanisms of TH signaling. The frog model boasts dramatic TH-dependent changes directly observable in free-living tadpoles with precise and easy experimental control of the TH response at developmental stages comparable to fetal stages in mammals. The hormones, their receptors, molecular mechanisms, and developmental roles of TH signaling are conserved to a high degree in humans and amphibians, such that with respect to developmental TH signaling "frogs are just little people that hop." The frog model is exceptionally illustrative of fundamental molecular mechanisms of in vivo TH action involving TH receptors, transcriptional cofactors, and chromatin remodeling. This review highlights the current need, recent successes, and future prospects using amphibians as a model to elucidate molecular mechanisms and functional roles of TH signaling during post-embryonic development.
PubMed ID: 28109053
Article link: Genesis
Genes referenced: carm1 crebbp klf9 ncor2 prmt1 slc7a5
Article Images: [+] show captions
|Figure 2. Comparison of mouse and frog models for study of in vivo TH signaling during development. Several unique aspects in frogs provide advantages for serving as a model to elucidate molecular mechanisms of TH signaling during development in vertebrates including humans. The key natural history assets for frogs are their exaggerated TH-dependent development, large clutch size, and free-living embryos/tadpoles giving rise to (1) ease of observation, tissue accessibility, and hormone manipulation, (2) lack of influence of maternal endocrine system on fetal development, and (3) natural development with unliganded TRs. The shorter generation time, historical advantage of mice for genome manipulation, and evolutionary closeness to humans are powerful aspects of the mouse model for TH signaling studies. However, with advances in gene disruption technology and sequencing of X. tropicalis and X. laevis genomes, the disparity in genomics tools between frogs and mice is closing.|