Abstract
BackgroundOrgan-specific, adult stem cells are essential for organ-homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development remains to be investigated. Frog metamorphosis offers an excellent opportunity to study the formation of adult stem cells as this process involves essentially the transformations of all larval tissues/organs into the adult form. Of particular interest is the remodeling of the intestine. Early studies in Xenopus laevis have shown that this process involves complete degeneration of the larval epithelium and de novo formation of adult stem cells through dedifferentiation of some larval epithelial cells. A major advantage of this metamorphosis model is its total dependence on thyroid hormone (T3). In an effort to identify genes that are important for stem cell development, we have previously carried out tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis.ResultsWe report the detailed characterization of one of the genes thus identified, the histidine ammonia-lyase (HAL) gene, which encodes an enzyme known as histidase or histidinase. We show that there are two duplicated HAL genes, HAL1 and HAL2, in both Xenopus laevis and Xenopus tropicalis, a highly related but diploid species. Interestingly, only HAL2 is highly upregulated by T3 and appears to be specifically expressed in the adult intestinal progenitor/stem cells while HAL1 is not expressed in the intestine during metamorphosis. Furthermore, when analyzed in whole animals, HAL1 appears to be expressed only during embryogenesis but not metamorphosis while the opposite appears to be true for HAL2.ConclusionsOur results suggest that the duplicated HAL genes have distinct functions with HAL2 likely involved in the formation and/or proliferation of the adult stem cells during metamorphosis.
Highlights
Organ-specific, adult stem cells are essential for organ-homeostasis and tissue repair and regeneration
These results suggest distinct, tissue-specific roles for the two histidine ammonia-lyase (HAL) genes during Xenopus development with HAL2 likely playing an important role in adult stem cell development and/or proliferation
The HAL gene was duplicated in Xenopus At the climax of metamorphosis in Xenopus laevis, the larval intestinal epithelial cells undergo apoptosis and adult epithelial progenitor/stem cells are formed and rapidly proliferate [8,19,36]
Summary
The HAL gene was duplicated in Xenopus At the climax of metamorphosis in Xenopus laevis, the larval intestinal epithelial cells undergo apoptosis and adult epithelial progenitor/stem cells are formed and rapidly proliferate [8,19,36]. Unlike HAL2, the HAL1 in situ probe failed to detect any signal in the intestine throughout metamorphosis, consistent with the RT-PCR results (data not shown) These findings suggest that HAL2 expression was specific to the adult. HAL1 and HAL2 have distinct temporal expression profiles during Xenopus development The presence of HAL1 cDNA sequence in the GenBank database suggests that HAL1 is expressed in some tissues and/or at some stages of development To investigate this possibility, we isolated total RNA from whole animals from embryonic stage 30 to the end of metamorphosis (stage 66) and carried out RT-PCR analysis by using the same primer sets as used above for their expression in the intestine. The results showed that HAL1 was highly expressed in embryos at stag 30 but was Figure 6 In situ hybridization analysis suggests specific expression of HAL2 in the proliferating adult intestinal progenitor/stem cells.
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