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Differentiation of Ameloblasts and Its Regulation by Epithelial-Mesenchymal Interactions
Published in Colin Robinson, Jennifer Kirkham, Roger Shore, Dental Enamel, 2017
The cuspal pattern of the tooth is established during the cap and subsequent early bell stages. Here a central regulatory role has been proposed for the enamel knot. This is a cluster of nondividing epithelial cells, including inner enamel epithelial cells, at the site of the first cusp in a cap stage tooth germ. Enamel knotlike structures are also present at bell stage and it is likely that these sites are involved in regulation of cusp development.1
Apoptosis: Cellular Signaling and Molecular Mechanisms
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Rosemary B. Evans, John A. Cidlowski
Additional proto-oncogenes which are required for progression of the cell cycle are the transcription factors c-Fos and c-Jun, which are transiently expressed in normally proliferating cells. Expression of these genes has also been studied during apoptosis. IL-6 withdrawal stimulates apoptosis in murine myeloma cell lines (7TD1 and B9) dependent on this cytokine.64 Transient expression of c-fos and c-jun was induced within 60 min after IL-6 deprivation of these cells. c-fos and c-jun expression was undetectable after 120 min and c-myc expression was not affected by this treatment. Antisense oligonucleotides complementary to either the c-jun or c-fos message led to increased survival of these growth factor deprived cells. Elegant studies performed using fos-lacZ transgenic mice in which c-fos expression was detected by β-galactosidase activity correlated in vivo c-fos expression with apoptosis in tissues which normally undergo extensive cell death.65 Expression of c-fos preceded apoptosis in atretic follicles/corpora lutea that were regressing but not in follicles containing an oocyte. c-fos expression was also seen in the heart valve cushion, enamel knot of teeth, and medial edge epithelium of the palate in mouse embryos at days 13 and 14 of embryogenesis, which are normal regions of apoptosis during this stage of development.65 These investigators also examined c-fos expression in murine fibroblasts derived from these transgenic mice after treatment with etoposide or phorbol esters. c-fos expression was detected in these cells prior to apoptotic cell death. Continuous expression of c-fos appears to lead to apoptosis; thus, the same transcription factor can induce proliferation or programmed cell death depending on the circumstances.
The protoconid: a key cusp in lower molars. Evidence from a recent modern human population
Published in Annals of Human Biology, 2022
José María Bermúdez de Castro, Cecilia García-Campos, Susana Sarmiento, María Martinón-Torres
In order to try to understand the final morphology of human Ms, let us give a brief overview of the morphogenesis of teeth. Mammalian tooth formation occurs through several stages of molecular interaction (e.g. Balic 2019; Chen et al. 2009; Ferguson et al. 1998; Zhang et al. 2005). Growth factors induce proliferation of the epithelium to form a dental lamina. After thickening of the epithelium, invagination occurs to form a tooth bud. The next stage is the folding of the epithelial layers to form the cap and bell stages, in which the primary enamel knot and the secondary enamel knots are differentiated (e.g. Li et al. 2013). The role of the primary enamel knot that forms at the end of the bud stage became known during the second half of the 1990s (Jernvall et al. 1994; Jernvall and Thesleff 2000; Thesleff et al. 2001). The primary enamel knot was first identified in the 1920s in cap stage tooth germs. It was recognised as a group or transitory cluster of non-dividing epithelial cells placed at the tip of the tooth bud (Orban 1928), and whose formation would be regulated by signals from the mesenchyme (Jernvall et al. 1998; Thesleff et al. 2001). The primary enamel knot becomes fully developed in the cap-stage dental epithelium and expresses at least ten different signalling molecules belonging to the BMP, FGF, SHH, and WNT families (Thesleff et al. 2001). Most of the cells of the enamel knots disappear by apoptosis once their function has been carried out (Thesleff et al. 2001). The primary enamel knot acts as a signalling centre that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps by inducing secondary enamel knots (e.g. Cho et al. 2007; Matalova et al. 2005; Pispa et al. 1999; Tucker et al. 2004).