Fig. 2

A molecular model of the action of thyroid hormone (TH) on the intestinal stem cell pathway was proposed. In intestinal stem cells, TH enters the nucleus and binds to TR to directly regulate the expression of HAS, HAL2, Mettl1, Mtfp1, DotiL and CLU genes. In addition, TH regulates the expression of multiple targets involved in the Wnt, Notch and hedgehog pathways. In the Wnt signalling pathway, the binding of TH to TR positively regulates the expression of Ctnnb1 and sFRP2 genes. In turn, Ctnnb1 and sFRP2 proteins allow β-catenin translocation to the nucleus by interacting with Wnt/β-catenin, where β-catenin forms a complex with transcription factors TCF/LEF, leading to increased expression of Wnt target genes, such as Cell cycle proteins D1/D2, Deiodinase 3 and c-Myc. In hedgehog signalling pathways, TH can act directly on Shh and promote enhanced transcription and expression of BMP4 and Foxl1