Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ - an immunohistochemical study.
Insulin-Like Growth Factor 2 (IGF-2) is a peptide hormone essential for prenatal growth and development. IGF-2 exerts its mitogenic effects via Insulin-Like Growth Factor 1 Receptor (IGF-1R), and is eliminated by binding to Insulin-Like Growth Receptor 2 (IGF-2R). IGF-2 is also negatively regulated by Phosphatase and Tensin Homolog (PTEN), a phosphatase mutated in various tumors. Not much is known about the interplay between these factors during human odontogenesis. In this study, expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN were analyzed by double immunofluorescence in incisor human tooth germs during the foetal period of development between the 7thand 20thgestational week. Throughout the investigated period, IGF-2 was mostly expressed in enamel organ, whereas mild to moderate expression of PTEN could be seen in dental papilla and parts of enamel organ. Expression of IGF-1R was ubiquitous and displayed strong intensity throughout the entire enamel organ. In contrast, expression of IGF-2R had rather erratic pattern in enamel organ and dental papilla alike. Expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN in highly proliferative cervical loops, as well as in differentiating pre-ameloblasts and pre-odontoblasts of cusp tip region during the early and late bell stages when enamel organ acquires definitive shape, indicate importance of these factors in crown morphogenesis of human incisor. Taken together, our data suggest the involvement of IGF-2, IGF-1R, IGF-2R and PTEN in temporo-spatial patterning of basic cellular processes (proliferation, differentiation) during normal tooth development. They are also relevant for improving knowledge of molecular basis of human odontogenesis.
a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia.
Darko
D
Kero
a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia.
Livia
L
Cigic
a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia.
Ivana
I
Medvedec Mikic
a Study Program of Dental Medicine , School of Medicine, University of Split , Split , Croatia.
Tea
T
Galic
b Dental Clinic Cubela , KMV Humskog bb , Mostar , Bosnia and Herzegovina.
Mladen
M
Cubela
c Department of Anatomy, Histology and Embriology , School of Medicine, University of Split , Split , Croatia.
Katarina
K
Vukojevic
c Department of Anatomy, Histology and Embriology , School of Medicine, University of Split , Split , Croatia.
Mirna
M
Saraga-Babic
D004848:Epithelium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007180:Incisor / Q000166:cytology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D014083:Tooth Germ / Q000196:embryology* / Q000378:metabolism*
C035170:IGF2 protein, human; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
IGF-1R; IGF-2; IGF-2R; IGF-axis; PTEN; differentiation; human tooth development; proliferation