Creacion De Dentina Por Celulas Señal Wnt

Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development
1. Lena Sarkar*†, 
2. Martyn Cobourne*†, 
3. Stuart Naylor‡§, 
4. Matthew Smalley‡,
5. Trevor Dale‡, and 
6. Paul T. Sharpe*¶
+Author Affiliations
1. *Department of Craniofacial Development, GKT Dental Institute, Guy's Hospital, London SE1 9RT, United Kingdom; ‡Institute ofCancer Research, The Toby Robins Breast Cancer Centre, 237 Fulham Road, London SW3 6JB, United Kingdom; and §Oxford BioMedica, Oxford Science Park, Oxford OX4 4GA, United Kingdom
1. Edited by Anthony P. Mahowald, University of Chicago, Chicago, IL, and approved February 3, 2000 (received for review December 3, 1999)
 
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AbstractInteractions between the Wnt (wingless) and hedgehog signaling pathways were first described as playing a role in establishing boundaries between ectodermal cells in Drosophila segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm must be formed to correctly position the sites of tooth formation. We describe a reciprocalrelationship between the expression of Wnt-7b in presumptive oral ectoderm andShh in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates. By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that Shh expression in the ectoderm and Ptcexpression in the underlyingectomesenchyme are down-regulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repressShh expression in oral ectoderm, thus maintaining the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt-7bspecifically affects Shh signaling.
The tooth is an example of an organ that arises from ectodermal and mesenchymal tissue components, the result of a series of interactions between oral ectoderm and the underlying neural crest-derived mesenchyme (1). Teeth are essential for survival in many vertebrates, and missing or misplaced teeth can have fatal consequences, causing some species to beunable to make use of available food supplies. It is critical, therefore, that the dentition develops correctly, with the required number and type of teeth developing in specific positions in the jaws. In mammals, teeth are formed from the first branchial arch derivatives, the mandibular and maxillary processes and the frontonasal process. The first morphological signs of tooth development occur atembryonic day (E)11.5 in mice with a thickening of the oral ectoderm that demarcates the sites of tooth formation as being distinctive from the neighboring oral ectoderm. This thickening invaginates further into the underlying ectomesenchyme during the next 2 days of development, with mesenchyme condensing around the resulting epithelial tooth buds. The nonthickened oral ectoderm develops into theepithelial cell lining of the mouth. From the bud stage of tooth development, the tooth germs progress to the cap stage, during which a putative signaling center, the enamel knot, forms (2, 3). From this stage, tooth germs progress through a well-characterized path of cytodifferentiation in which the condensing mesenchyme, termed the dental papilla, gives rise to the tooth pulp and thedentine-producing odontoblasts. The epithelium differentiates into enamel-secreting ameloblasts that are a cell type unique to teeth.
Sonic hedgehog (Shh) is a member of the family of hedgehog-secreted peptides, of which Drosophila hedgehog (hh) was the first to be identified (4–6). Genes involved in the hedgehog signaling pathway, namely Patched (Ptc), Smoothened (Smo), Gli genes and protein kinase A have...