| First Author | Sirakov M | Year | 2015 |
| Journal | Development | Volume | 142 |
| Issue | 16 | Pages | 2764-74 |
| PubMed ID | 26286942 | Mgi Jnum | J:239787 |
| Mgi Id | MGI:5829639 | Doi | 10.1242/dev.121962 |
| Citation | Sirakov M, et al. (2015) The thyroid hormone nuclear receptor TRalpha1 controls the Notch signaling pathway and cell fate in murine intestine. Development 142(16):2764-74 |
| abstractText | Thyroid hormones control various aspects of gut development and homeostasis. The best-known example is in gastrointestinal tract remodeling during amphibian metamorphosis. It is well documented that these hormones act via the TR nuclear receptors, which are hormone-modulated transcription factors. Several studies have shown that thyroid hormones regulate the expression of several genes in the Notch signaling pathway, indicating a possible means by which they participate in the control of gut physiology. However, the mechanisms and biological significance of this control have remained unexplored. Using multiple in vivo and in vitro approaches, we show that thyroid hormones positively regulate Notch activity through the TRalpha1 receptor. From a molecular point of view, TRalpha1 indirectly controls Notch1, Dll1, Dll4 and Hes1 expression but acts as a direct transcriptional regulator of the Jag1 gene by binding to a responsive element in the Jag1 promoter. Our findings show that the TRalpha1 nuclear receptor plays a key role in intestinal crypt progenitor/stem cell biology by controlling the Notch pathway and hence the balance between cell proliferation and cell differentiation. |
