Molar tooth development in caspase-3 deficient mice.

Tooth morphogenesis is accompanied by apoptotic events which show restricted temporospatial patterns suggesting multiple roles in odontogenesis. Dental apoptosis seems to be caspase dependent and caspase-3 has been shown to be activated during dental apoptosis.Caspase-3 mutant mice on different genetic backgrounds were used to investigate alterations in dental apoptosis and molar tooth morphogenesis. Mouse embryos at E15.5 were analyzed to reveal any changes in enamel knots, which are transient structures eliminated by apoptosis. In caspase-3(-/-) mice on the B57BL/6 background, disorganization of the epithelium was found in the original primary enamel knot area and confirmed by altered expression of Shh. Despite this early defect in molar tooth development, these mutants showed correct formation of secondary enamel knots as indicated by Fgf-4 expression. Analyses of adult molar teeth did not reveal any major alterations in tooth shape, enamel structure or pattern when compared to heterozygote littermates. In caspase-3(-/-) mice on the 129X1/SvJ background, no defects in tooth development were found except the position of the upper molars which developed more posteriorly in the oral cavity. This is likely, however, to be a secondary defect caused by a physical squashing of the face by the malformed brain. The results suggest that although caspase-3 becomes activated and may be essential for dental apoptosis, it does not seem fundamental for formation of normal mineralised molar teeth.

[1]  F. Kovářů,et al.  Caspase 3 activation in the primary enamel knot of developing molar tooth. , 2006, Physiological research.

[2]  P. T. Sharpe,et al.  Cell lineage of primary and secondary enamel knots , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[3]  C. Martínez-A,et al.  A generalized caspase inhibitor disrupts early mammalian development. , 2005, The International journal of developmental biology.

[4]  Sharad Kumar.  Migrate, Differentiate, Proliferate, or Die: Pleiotropic Functions of an Apical "Apoptotic Caspase" , 2004, Science's STKE.

[5]  Hyung Don Ryoo,et al.  Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. , 2004, Developmental cell.

[6]  J. Segalés,et al.  Apoptosis in normal lymphoid organs from healthy normal, conventional pigs at different ages detected by TUNEL and cleaved caspase-3 immunohistochemistry in paraffin-embedded tissues. , 2004, Veterinary immunology and immunopathology.

[7]  P. Sharpe,et al.  Death in the Life of a Tooth , 2004, Journal of dental research.

[8]  N. Gulyaeva,et al.  Non-apoptotic Functions of Caspase-3 in Nervous Tissue , 2003, Biochemistry (Moscow).

[9]  A. Akamine,et al.  Localization of Activated Caspase-3-positive and Apoptotic Cells in the Developing Tooth Germ of the Mouse Lower First Molar , 2004, The Histochemical Journal.

[10]  E. Fujita,et al.  Region of caspase-3 activation and programmed cell death in the early development of the mouse forebrain. , 2003, Brain research. Developmental brain research.

[11]  K. Schulze-Osthoff,et al.  Non-apoptotic functions of caspases in cellular proliferation and differentiation. , 2003, Biochemical pharmacology.

[12]  K. Nakanishi,et al.  Caspase-9 Takes Part in Programmed Cell Death in Developing Mouse Kidney , 2003, Nephron Experimental Nephrology.

[13]  R. Flavell,et al.  Strain‐Dependent Neurodevelopmental Abnormalities in Caspase‐3‐Deficient Mice , 2002, Journal of neuropathology and experimental neurology.

[14]  Yigong Shi,et al.  Mechanisms of caspase activation and inhibition during apoptosis. , 2002, Molecular cell.

[15]  S. Korsmeyer,et al.  Mouse models of cell death , 2001, Nature Genetics.

[16]  J. Vonesch,et al.  Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse. , 2000, The International journal of developmental biology.

[17]  R. Flavell,et al.  Divinations and surprises: genetic analysis of caspase function in mice. , 2000, Experimental cell research.

[18]  C. Reutelingsperger,et al.  In situ detection of apoptosis in dental and periodontal tissues of the adult mouse using annexin-V-biotin , 2000, Histochemistry and Cell Biology.

[19]  M. Lenardo,et al.  Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies. , 2000, Journal of cell science.

[20]  R. Flavell,et al.  Caspase knockouts: matters of life and death , 1999, Cell Death and Differentiation.

[21]  P. Williamson,et al.  Regulation of phosphatidylserine exposure and phagocytosis of apoptotic T lymphocytes , 1999, Cell Death and Differentiation.

[22]  E. Marani,et al.  Spatiotemporal distribution of dying neurons during early mouse development , 1999, The European journal of neuroscience.

[23]  M. Rosenfeld,et al.  Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development. , 1999, Development.

[24]  S H Kaufmann,et al.  Mammalian caspases: structure, activation, substrates, and functions during apoptosis. , 1999, Annual review of biochemistry.

[25]  J. Boyer,et al.  Caspase-3 controls both cytoplasmic and nuclear events associated with Fas-mediated apoptosis in vivo. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Momoi,et al.  Detection of activated caspase-3 (CPP32) in the vertebrate nervous system during development by a cleavage site-directed antiserum. , 1998, Brain research. Developmental brain research.

[27]  Keisuke Kuida,et al.  Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9 , 1998, Cell.

[28]  José Luis de la Pompa,et al.  Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo , 1998, Cell.

[29]  J. Beckmann,et al.  Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. , 1998, Immunity.

[30]  S. Lowe,et al.  Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. , 1998, Genes & development.

[31]  S. Keränen,et al.  The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. , 1998, Development.

[32]  N. Thornberry,et al.  Caspases: killer proteases. , 1997, Trends in biochemical sciences.

[33]  R. Gascoyne,et al.  Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. , 1997, Cancer research.

[34]  Keisuke Kuida,et al.  Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice , 1996, Nature.

[35]  J. Vonesch,et al.  Mouse molar morphogenesis revisited by three-dimensional reconstruction. II. Spatial distribution of mitoses and apoptosis in cap to bell staged first and second upper molar teeth. , 1996, The International journal of developmental biology.

[36]  A. Vaahtokari,et al.  Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4. , 1996, Development.

[37]  B. Barres,et al.  Programmed cell death and the control of cell survival: lessons from the nervous system. , 1993, Science.