NIH Research Festival
FARE Award Winner
The thyroid hormone (T3)-dependent frog metamorphosis resembles mammalian postembryonic development and offers a unique opportunity to study how adult stem cells are developed, largely due the ability to manipulate the externally developing frog embryo. In particular, the remodeling of the intestine during metamorphosis mimics neonatal maturation of mammalian intestine, the well-characterized organ for studying adult stem cells due to the life-long epithelial self-renewing system. Our earlier studies have shown that the formation of the adult intestine during Xenopus metamorphosis involves complete degeneration of the larval epithelium and de novo formation of adult stem cells. A tissue-specific microarray analysis of intestinal gene expression during metamorphosis has identified a number of novel candidate stem cell genes. Among them is the amidohydrolase domain containing 1 (AMDHD1) gene, which encodes an enzyme involved in the catabolism of histidine. In this study, we show that AMDHD1 is exclusively expressed in the proliferating adult intestinal epithelial stem cells during metamorphosis. We further provide evidence that T3 activates AMDHD1 gene expression directly at the transcription level through T3 receptor binding to the AMDHD1 gene in the intestine. These together with our earlier finding that histidine ammonia-lyase (HAL) gene in histidine catabolic pathway is similarly regulated by T3 in the intestine suggest that histidine catabolism plays a critical role in the formation of adult intestinal stem cells during metamorphosis. Thus, our findings provide the first evidence for the involvement of metabolic pathways in intestinal adult stem cell formation and likely metabolic disorders in intestinal diseases as well.
Scientific Focus Area: Developmental Biology
This page was last updated on Friday, March 26, 2021