The Genetic Control of Early Tooth Development

Abstract

Most vertebrate organs begin their initial formation by a common, developmentally conserved pattern of inductive tissue interactions between two tissues. The developing tooth germ is a prototype for such inductive tissue interactions and provides a powerful experimental system for elucidation of the genetic pathways involved in organogenesis. Members Msxl is required for the transmission of Bmp4 expression from dental epithelium to mesenchyme and also for Lefi expression.In addition, we consider the role of other signaling molecules in the epithelial-mesenchymal interactions leading to tooth formation, the role that transcription factors such as Msx play in the propagation of inductive signals, and the role of extracellular matrix. Last, as a unifying mechanism to explain the disparate tooth phenotypes in Msxl-and Msx2-deficient mice, we propose that later steps in tooth morphogenesis molecularly resemble those in early tooth development. )from a series of instructive and permissive cell-cell interactions (Saxen, 1977a;Wessells, 1977). The determination of the mesoderm and neural plate in vertebrate embryos is referred to as primary induction (Spemann and Mangold, 1924), and is followed by a series of secondary inductive events which further regulate embryonic organ development. Over the last decade, the application of molecular biology to problems in vertebrate development has revealed a considerable amount of information about the nature of the inductive signals which are exchanged between tissue layers during inductive tissue interactions (reviewed in Jessell and Melton, 1992;Kessler and Melton, 1994). This review focuses specifically on the genetic hierarchies which appear to operate during early tooth development, on the nature of the inductive signals which are exchanged between the dental epithelium and mesenchyme, and on the role that one particular class of transcription factors, those belonging to the Msx family of homeobox genes, plays in controlling these inductive tissue interactions. Several excellent recent reviews on tooth development are also available (Ruch, 1995;Sharpe, 1995;Thesleff et al., 1995a Thesleff et al., ,b, 1996 Thesleff and Sahlberg, 1996), and a "tooth gene expression database" is also available on the Internet (http://honeybee.helsinki.fi/toothexp).The dentition not only constitutes a major component of the mammalian craniofacial system, but also provides a powerful and potentially general model for the study of organ development. The possibility of in vitro cultivation, access to cytological and molecular studies, the clear delineation of epithelial and mesenchymal components, the easily distinguished characteristics of ameloblasts and odontoblasts, and the anteroposterior, position-dependent pattern of dentition make the devel-4

Spatiotemporal distribution of apoptosis during normal cloacal development in mice

“…Numerous reports have suggested that apoptosis is associated with down-or upregulation of various developmental regulatory genes (Wyllie, 1987;Buttyan et al, 1988;Collins et al, 1994;Maas and Bei, 1997;Kerä nen et al, 1999). Some evidence even suggests that all cells undergo apoptosis by default unless they are rescued by survival factors (Raff, 1992;Steller, 1995).…”

Study of Pax6 mutant rat revealed the association between upper incisor formation and midface formation

“…Signaling from the mesenchyme is required for further tooth morphogenesis. Several secreted signaling molecules (Bmp2,Bmp4,Fgf4,Fgf8,and Shh) and transcription factors (Lef1,Msx1,Msx2,Pitx2,and Pax9) have been shown to play important roles in these processes (Maas and Bei, 1997;Neubü ser et al, 1997;Hardcastle et al, 1998;Thesleff and Mikkola, 2002).…”

Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the Developing Mouse First Lower Molar

“…The functional differentiation of ameloblasts is initiated 24 hr later. Signaling molecules, which belong to several distinct families including BMPs, FGFs, and WNTs, control each of these steps (for review see Maas and Bei 1997;Tucker and Sharpe 1999;Thesleff and Mikkola 2002).…”