Dr Heiko Peters
Reader in Mammalian Genetics
- Email: heiko.peters@ncl.ac.uk
- Telephone: 0191 241 8622
- Fax: 0191 241 8666
- Address: Institute of Human Genetics
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
Research Interests
Genetic control of craniofacial and tooth development
During embryogenesis, the induction and morphogenesis of most organs is regulated by a series of reciprocal tissue interactions, typically between epithelium and mesenchyme. These interactions involve modifications of gene expression patterns in both tissue compartments to co-ordinate growth, shape and differentiation of the forming organ. Using the developing tooth of the mouse as the primary model system, our laboratory investigates the molecular “cross-talk” that regulates these early tissue interactions.
We generate mouse models by means of homologous recombination in embryonic stem cells and combine phenotype analyses with genome-wide expression profiling and organ culture experiments. Our aim is to understand the dynamics within the genetic networks that regulate epithelial-mesenchymal interactions during the early phases of organogenesis.Our work currently concentrates on the transcription factor Pax9, which we have shown to function as a key regulator for the development of a variety of organs, including secondary palate and teeth. Heterozygous mutations in the human PAX9 gene have subsequently been demonstrated in a number of studies to dominantly cause missing teeth. Paradoxically, the heterozygous Pax9 mutation in mice does not result in obvious tooth defects, prompting us to develop a new mouse model in which the gene dosage of Pax9 is gradually reduced. Specific combinations of these alleles cause - as in humans – hypodontia. We now use these new models to investigate the molecular and cellular processes that cause hypodontia and establish the size of the mammalian dentition.
Similar to missing teeth, orofacial clefting such as cleft lip and cleft palate often occur sporadically and do not follow an obvious Mendelian inheritance. This is generally explained by interactions involving mutations in several genes, which are combined by transmission from unaffected parents. However, identification of candidate genes in humans had limited success. Using a panel of different mouse mutants we are currently addressing this problem by combining mutations of potential clefting susceptibility genes in oligogenic mouse model systems.
Co-workers
Ralf Kist BSc PhD
Wellcome Trust Research Associate
Mitsushiro Nakatomi BSc DDS PhD
MRC Research Associate
Liming Wang BSc
Self funded PhD student
Selected Publications
- Nakatomi M; Wang XP; Key D; Lund JJ; Turbe-Doan A; Kist R; Aw A; Chen Y; Maas RL; Peters H. Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Developmental Biology 2010, epub ahead of print.
- Wang J; Qin R; Ma Y; Wu HY; Peters H; Tyska M; Shaheen NJ; Chen XX. Differential gene expression in normal esophagus and Barrett's esophagus. Journal of Gastroenterology 2009, 44(9), 897-911.
- Greenall A; Lei GY; Swan DC; James K; Wang LM; Peters H; Wipat A; Wilkinson DJ; Lydall D. A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD(+) biosynthetic gene BNA2 in chromosome end protection. Genome Biology 2008, 9(10), R146.
- Wurtz T; Houari S; Mauro N; MacDougall M; Peters H; Berdal A. Fluoride at non-toxic dose affects odontoblast gene expression in vitro. Toxicology 2008, 249(1), 26-34.
- Paakkonen V; Bleicher F; Carrouel F; Vuoristo JT; Salo T; Wappler I; Couble ML; Magloire H; Peters H; Tjaderhane L. General expression profiles of human native odontoblasts and pulp-derived cultured odontoblast-like cells are similar but reveal differential neuropeptide expression levels. Archives of Oral Biology 2008, 54(1), 55-62.
- Ehrmann I; Dalgliesh C; Tsaousi A; Paronetto MP; Heinrich B; Kist R; Cairns P; Li W; Mueller C; Jackson M; Peters H; Nayernia K; Saunders P; Mitchell M; Stamm S; Sette C; Elliott DJ. Haploinsufficiency of the germ cell-specific nuclear RNA binding protein hnRNP G-T prevents functional spermatogenesis in the mouse. Human Molecular Genetics 2008, 17(18), 2803-2818.
