Development and renewal of ectodermal organs

Background: Interactions between cells constitute a key mechanism in the regulation of embryonic development. We explore the cell interactions involved in the development and renewal of organs forming as appendages of the surface ectoderm. Our focus is in the formation of teeth, hairs and some glands, and the roles of signaling networks mediating intercellular communication. We examine how these networks regulate the patterns, numbers, sizes, shapes and renewal of ectodermal organs. We use mouse models and organ culture techniques to study the functions of conserved signal pathways including FGF, TGF, Hedgehog, Wnt and Ectodysplasin (Eda). Some of the mice are models for human syndromes such as ectodermal dysplasias and tooth agenesis.

Current progress and aims
1) Our particular interest is the formation of placodes initiating the development of all ectodermal appendages. We have shown that stimulation of Wnt and Eda signaling induces extra placodes resulting in the formation of extra teeth, whiskers and hairs. We have identified a number of Eda targets which include both positive and negative effectors of other conserved signal pathways, and several mouse lines are currently used to examine the signaling networks.

2) We are focusing increasingly on the mechanisms of tooth renewal. We discovered in 1999 a stem cell niche in continuously growing mouse teeth and this has allowed research on dental stem cell regulation. Our work on these epithelial stem cells has revealed that their maintenance, proliferation and differentiation is regulated by a complex signaling network involving several TGFβ and FGF signals, and that microRNAs are important modulators of this network. We have identified Sox2 as the first marker of these stem cells and demonstrated that they can give rise to all epithelial lineages in teeth.The aim of our current work is to characterize the dental stem cells and their progeny, and to explore the possibilities to generate teeth using these cells. The results or our research may have clinical implica­tions in the diagnosis, prevention and treatment of congenital defects as well as in the design of regenerative therapies.