Sonic hedgehog regulates growth and morphogenesis of the tooth

During mammalian tooth development, the oral ectoderm and mesenchyme coordi nate their growth and differentiation to give rise to organs with precise s hapes, sizes and functions. The initial ingrowth of the dental epithelium a nd its associated dental mesenchyme gives rise to the tooth bud. Next, the epithelial component folds to give the tooth its shape. Coincident with thi s process, adjacent epithelial and mesenchymal cells differentiate into ena mel-secreting ameloblasts and dentin-secreting odontoblasts, respectively. Growth, morphogenesis and differentiation of the epithelium and mesenchyme are coordinated by secreted signaling proteins. Sonic hedgehog (Shh) encode s a signaling peptide which is present in the oral epithelium prior to imag ination and in the tooth epithelium throughout its development. We have add ressed the role of Shh in the developing tooth in mouse by using a conditio nal allele to remove Shh activity shortly after ingrowth of the dental epit helium. Reduction and then loss of Shh function results in a cap stage toot h rudiment in which the morphology is severely disrupted, The overall size of the tooth is reduced and both the lingual epithelial imagination and the dental cord are absent. However, the enamel knot, a putative organizer of crown formation, is present and expresses Fgf4, Wnt10b, Bmp2 and Lef1, as i n the wild type. At birth, the size and the shape of the teeth are severely affected and the polarity and organization of the ameloblast and odontobla st layers is disrupted, However, both dentin- and enamel-specific markers a re expressed and a large amount of tooth-specific extracellular matrix is p roduced, This observation was confirmed by grafting studies in which tooth rudiments were cultured for several days under kidney capsules. Under these conditions, both enamel and dentin were deposited even though the enamel a nd dentin layers remained disorganized. These studies demonstrate that Shh regulates growth and determines the shape of the tooth. However, Shh signal ing is not essential for differentiation of ameloblasts or odontoblasts.