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Figure 1 | Cell & Bioscience

Figure 1

From: The development of the adult intestinal stem cells: Insights from studies on thyroid hormone-dependent amphibian metamorphosis

Figure 1

T3-dependent intestinal remodeling during Xenopus laevis metamorphosis serves as a model to study adult organ-specific stem cell development in vertebrates. Top: In premetamorphic tadpoles, there is little or no T3 and the intestine has a simple structure with only a single fold, the typhlosole. This structure is similar to the mammalian embryonic intestine. At the metamorphic climax when T3 level is high, the larval epithelial cells begin to undergo apoptosis, as indicated by the circles. Concurrently, the proliferating adult progenitor/stem cells develop de novo from larval epithelial cells through dedifferentiation, as indicated by black dots. By the end of metamorphosis, the newly differentiated adult epithelial cells form a multiply folded epithelium, similar to mammalian adult intestines. This process is entirely controlled by T3 and can be induced even in organ cultures of tadpole intestine with T3 treatment. In mammals, the intestine undergoes postembryonic maturation into the adult form around or shortly after birth when T3 levels are also high. Thus, intestinal metamorphosis offers a unique opportunity to study the development of adult intestinal stem cells. Bottom: T3 functions by regulating gene transcription through TRs. In the absence of T3 (as in premetamorphic tadpole), TR forms heterodimers with RXR and the heterodimer binds to target gene promoters to repress their expression by recruiting corepressor complexes containing the related proteins N-CoR or SMRT and histone deacetylases. When T3 is present, the corepressor complexes are released upon T3 binding to TR, and simultaneously coactivator complexes such as those containing SRC, p300, and PRMT1, are recruited to activate target gene expression. SRC and p300 are histone acetyltransferases and PRMT1 is a histone methyltransferase. The coactivator complexes will modify histones and activate gene expression to induce metamorphosis.

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