Development and Synthesis of Cranial Placodes

Abstract

Due to the diversity of mutations that affect their development, both sensory and non-sensory cranial placodes constitute powerful models for developmental biology. We have used mouse models and human diseases to explore the gene regulatory networks (GRNs) that control the development and differentiation of two ectodermal placodes, the ocular lens and the molar tooth. In lens and tooth development, Pax genes play central roles in the regulation of downstream GRNs. To further elucidate these GRNs, we have performed dynamic microarray studies on wild type and mutant mouse embryos. In the developing lens placode, one finding is that the RNA granule component, Tdrd7, plays a key role downstream of Pax6 in the post-transcriptional regulation of lens fiber cell differentiation. In the dental, or odontogenic placode, the GRN is structured such that activation of a single signaling pathway (canonical Wnt) is sufficient to induce the formation of fully mineralized supernumerary teeth, even in adult mice. Overall, these studies suggest that GRNs have been redeployed, with potentially modest variation, for the development of different cranial placodes and tissues. Furthermore, both the lens and tooth systems appear amenable to efforts aimed at using the information encoded in their respective GRNs to induce placode and subsequent stage tissue synthesis from stem cells. This work was supported by the NEI, NIDCR and NICHD.