Thyroid hormone induction of adult stem cell formation during postembryonic development: An essential role of sonic hedgehog signaling mediated cell‐cell interaction

Abstract

Adult organ‐specific stem cells are essential for organ homeostasis and tissue repair and regeneration, but the underlying mechanism for their development is unclear. Intestinal remodeling during frog metamorphosis offers a unique opportunity to study the formation of such stem cells during vertebrate development. During the transition from an herbivorous tadpole to a carnivorous frog, the intestine is completely remodeled with the larval epithelial cells undergo apoptosis and are replaced by adult epithelial cells developed de novo. The entire metamorphic process is under the control of thyroid hormone. We have shown that adult epithelial stem cells are induced by thyroid hormone through dedifferentiation of some larval epithelial cells. Interestingly, thyroid hormone action in larval epithelial cells alone can induce the formation of putative precursors of the adult stem cells, the formation of the stem cells and their eventual differentiation into the adult epithelium require thyroid hormone action in the nonepithelial tissues as well. This latter action is likely through the connective tissue, leading to the formation of proper stem cell niche. We will further provide evidence that sonic hedgehog signaling, which is induced by thyroid hormone, is one important pathway that mediates the cell‐cell interaction for the formation of the adult intestinal stem cells during this process.