NOTCH SIGNALLING IN THE TEETH OF PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE (PACAP)-DEFICIENT MICE
Daniel Balazs Fulop1, 1, Balazs Sandor1, 2, Eszter Szentleleky3, Edina Karanyicz3, Dora Reglodi1, Roza Zakany3, Tamas Juhasz3, Andrea Tamas1
1 Department of Anatomy, MTA-PTE PACAP Research Team, Centre for Neuroscience, University of Pecs, Medical School, Hungary 2Department of Dentistry, Oral and Maxillofacial Surgery, University of Pecs, Medical School, Hungary 3Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Hungary.
PACAP is a neuropeptide affecting the development and function of the nervous system and several other organs. Its role in tooth development has been already proven, e.g. it influences the Shh (Sonic hedgehog) pathway. We have shown that tooth mineralisation and organic composition are disturbed in PACAP-deficient animals. The role of Notch signalling in tooth development is also well-described. We planned to elucidate the possible connection between PACAP and Notch signalling during tooth development. We applied immunohistochemistry for Notch receptors (Notch1,2,3,4), ligands (DLL1,3,4, Jagged1,2) and intracellular target molecules (CSL, TACE, Numb) in sections of molar teeth of wild type, homozygous and heterozygous PACAP-deficient mice. We have measured the immunopositivity of Notch signalling pathway molecules in the enamel producing ameloblast cells and dentin producing odontoblast cells. We found elevated Notch2 receptor and DLL1 expression in the ameloblast cells of PACAP-deficient mice compared to the wild-type ones. CSL yielded similar results both in the ameloblast and odontoblast cells. Jagged1 ligand showed higher expression in the odontoblast cells of homozygous PACAP-deficient mice than in wild-type mice. The other elements of Notch signalling have not shown significant differences. Our results showed that the lack of PACAP leads to upregulation of several elements of the Notch signalling pathway in the odontoblast and ameloblast cells. We presume Shh dependent and independent processes. Notch signalling, similarly to PACAP, is responsible for affecting cell proliferation and apoptosis. We hypothesize that Notch could serve as a salvage pathway in the case of the lack of endogenous PACAP.