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Autophagy appears during the development of the mouse lower first molar

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Abstract

Odontogenesis consists of a series of consecutive tooth morphogenesis stages, in which apoptosis is involved to eliminate the unnecessary cells. Autophagy, a lysosome or endosome-mediated self-degradation process, is indicated to participate in embryogenesis and tissue morphogenesis associated with apoptosis. This study hypothesized that autophagy may be involved and associated with apoptosis in odontogenesis. The transcripts of autophagy-related genes (Atg5, Atg7, and Atg12) were positively detected in tooth germs at embryonic day (E) 14.5 and postnatal day (P) 5.5 by quantitative real-time PCR. The protein expression of Atg5–Atg12 conjugate and lipidation of LC3 (microtubule-associated protein 1 light chain 3, autophagic marker) were revealed in the developing tooth germs by western blot. Meanwhile, LC3 was immunolocalized in the enamel organ and dental papilla at embryonic stages (E13.5–E18.5), especially stage E14.5 cervical loop and the PEK that facing the mesenchyme. At postnatal stages (P1.5–P15.5), besides the dental epithelium cells, LC3 was detected in the differentiating and differentiated odontoblasts, dental follicle cells, and Hertwig’s epithelium root sheath cells. Moreover, double-immunofluorescence analysis revealed the partial colocalization of LC3 and TUNEL signal in the E14.5 PEK that facing the mesenchyme, the E16.5 stratum intermedium and outer enamel epithelium, the P5.5 stratum intermedium and stellate reticulum. Nevertheless, LC3 was also found in non-apoptotic cells. Furthermore, the transmission electron microscopic images revealed the presence of autophagy, as well as the partial colocalization of autophagic vacuoles and apoptotic nuclei during tooth development. Our findings imply the developmental appearance of autophagy and its partial colocalization with apoptosis during odontogenesis.

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References

  • Bamber BA, Rowland AM (2006) Shaping cellular form and function by autophagy. Autophagy 2:247–249

    PubMed  CAS  Google Scholar 

  • Berry DL, Baehrecke EH (2007) Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 131:1137–1148

    Article  PubMed  CAS  Google Scholar 

  • Caton J, Tucker AS (2009) Current knowledge of tooth development: patterning and mineralization of the murine dentition. J Anat 214:502–515

    Article  PubMed  Google Scholar 

  • Cecconi F, Di Bartolomeo S, Nardacci R, Fuoco C, Corazzari M, Giunta L, Romagnoli A, Stoykova A, Chowdhury K, Fimia GM, Piacentini M (2007) A novel role for autophagy in neurodevelopment. Autophagy 3:506–508

    PubMed  CAS  Google Scholar 

  • Couve E (1986) Ultrastructural changes during the life cycle of human odontoblasts. Arch Oral Biol 31:643–651

    Article  PubMed  CAS  Google Scholar 

  • Couve E, Schmachtenberg O (2011) Autophagic activity and aging in human odontoblasts. J Dent Res 90:523–528

    Article  PubMed  CAS  Google Scholar 

  • Di Bartolomeo S, Nazio F, Cecconi F (2010) The role of autophagy during development in higher eukaryotes. Traffic 11:1280–1289

    Article  PubMed  Google Scholar 

  • Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A (2009) Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ 16:966–975

    Article  PubMed  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  PubMed  CAS  Google Scholar 

  • Eskelinen EL (2005) Maturation of autophagic vacuoles in Mammalian cells. Autophagy 1:1–10

    Article  PubMed  CAS  Google Scholar 

  • Eskelinen EL (2008) To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells. Autophagy 4:257–260

    PubMed  Google Scholar 

  • Gajewska M, Gajkowska B, Motyl T (2005) Apoptosis and autophagy induced by TGF-B1 in bovine mammary epithelial BME-UV1 cells. J Physiol Pharmacol 56(Suppl 3):143–157

    PubMed  Google Scholar 

  • Galluzzi L, Vicencio JM, Kepp O, Tasdemir E, Maiuri MC, Kroemer G (2008) To die or not to die: that is the autophagic question. Curr Mol Med 8:78–91

    Article  PubMed  CAS  Google Scholar 

  • Holt SV, Wyspianska B, Randall KJ, James D, Foster JR, Wilkinson RW (2011) The development of an immunohistochemical method to detect the autophagy-associated protein LC3-II in human tumor xenografts. Toxicol Pathol 39:516–523

    Article  PubMed  CAS  Google Scholar 

  • Jernvall J, Thesleff I (2000) Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev 92:19–29

    Article  PubMed  CAS  Google Scholar 

  • Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728

    Article  PubMed  CAS  Google Scholar 

  • Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290:1717–1721

    Article  PubMed  CAS  Google Scholar 

  • Klionsky DJ, Cuervo AM, Seglen PO (2007) Methods for monitoring autophagy from yeast to human. Autophagy 3:181–206

    PubMed  CAS  Google Scholar 

  • Le Bot N (2007) Autophagy: a new regulator of development. Nat Cell Biol 9(7):741

    Article  PubMed  Google Scholar 

  • Matalova E, Svandova E, Tucker AS (2011) Apoptotic signaling in mouse odontogenesis. OMICS 16:60–70

    Article  PubMed  Google Scholar 

  • Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36(12):2491–2502

    Article  PubMed  CAS  Google Scholar 

  • Mizushima N, Levine B (2010) Autophagy in mammalian development and differentiation. Nat Cell Biol 12:823–830

    Article  PubMed  CAS  Google Scholar 

  • Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW (2007) A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 204(1):25–31

    Article  PubMed  CAS  Google Scholar 

  • Rubinsztein DC, Marino G, Kroemer G (2011) Autophagy and aging. Cell 146:682–695

    Article  PubMed  CAS  Google Scholar 

  • Setkova J, Lesot H, Matalova E, Witter K, Matulova P, Misek I (2006) Proliferation and apoptosis in early molar morphogenesis– voles as models in odontogenesis. Int J Dev Biol 50(5):481–489

    PubMed  Google Scholar 

  • Setkova J, Matalova E, Sharpe PT, Misek I, Tucker AS (2007) Primary enamel knot cell death in Apaf-1 and caspase-9 deficient mice. Arch Oral Biol 52:15–19

    Article  PubMed  CAS  Google Scholar 

  • Shigemura N, Kiyoshima T, Sakai T, Matsuo K, Momoi T, Yamaza H, Kobayashi I, Wada H, Akamine A, Sakai H (2001) Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar. Histochem J 33:253–258

    Article  PubMed  CAS  Google Scholar 

  • Srinivas V, Shapiro IM (2006) Chondrocytes embedded in the epiphyseal growth plates of long bones undergo autophagy prior to the induction of osteogenesis. Autophagy 2:215–216

    PubMed  CAS  Google Scholar 

  • Terman A, Brunk UT (2005) Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc Res 68:355–365

    Article  PubMed  CAS  Google Scholar 

  • Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211:134–143

    Article  PubMed  CAS  Google Scholar 

  • Thesleff I (2003) Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 116:1647–1648

    Article  PubMed  CAS  Google Scholar 

  • Thorburn A (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13:1–9

    Article  PubMed  CAS  Google Scholar 

  • Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534

    Article  PubMed  CAS  Google Scholar 

  • Vaahtokari A, Aberg T, Thesleff I (1996) Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4. Development 122(1):121–129

    PubMed  CAS  Google Scholar 

  • Vellai T, Takacs-Vellai K, Sass M, Klionsky DJ (2009) The regulation of aging: does autophagy underlie longevity? Trends Cell Biol 19:487–494

    Article  PubMed  CAS  Google Scholar 

  • Vessoni AT, Muotri AR, Okamoto OK (2012) Autophagy in stem cell maintenance and differentiation. Stem Cells Dev 21(4):513–520

    Article  PubMed  CAS  Google Scholar 

  • Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Klionsky DJ (2009) An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 335:1–32

    Article  PubMed  CAS  Google Scholar 

  • Yorimitsu T, Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12(Suppl 2):1542–1552

    Article  PubMed  CAS  Google Scholar 

  • Zaki AE, MacRae EK (1977) Fine structure of the secretory and nonsecretory ameloblasts in the frog. I. Fine structure of the secretory ameloblasts. Am J Anat 148:161–193

    Article  PubMed  CAS  Google Scholar 

  • Zang L, Xu Q, Ye Y, Li X, Liu Y, Tashiro S, Onodera S, Ikejima T (2012) Autophagy enhanced phagocytosis of apoptotic cells by oridonin-treated human histocytic lymphoma U937 cells. Arch Biochem Biophys 518:31–41

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the grants from the National Natural Science Foundation of China (304163113); National 973 project of China (2010CB534915).

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Authors and Affiliations

  1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, 430079, China

    Jing-wen Yang, Ling-xin Zhu, Guo-hua Yuan, Yang-xi Chen, Li Zhang, Lu Zhang & Zhi Chen

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  1. Jing-wen Yang
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  2. Ling-xin Zhu
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  3. Guo-hua Yuan
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  4. Yang-xi Chen
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Correspondence to Lu Zhang or Zhi Chen.

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Yang, Jw., Zhu, Lx., Yuan, Gh. et al. Autophagy appears during the development of the mouse lower first molar. Histochem Cell Biol 139, 109–118 (2013). https://doi.org/10.1007/s00418-012-1016-2

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