DEPARTMENT OF TERATOLOGY

Head:

Publications

Miroslav Peterka, M.D., D.Sc.
Email: peterka@biomed.cas.cz
tel: +420241062604

Laboratory of Embryogenesis

Head: Miroslav Peterka, M.D., D.Sc.
Email: peterka@biomed.cas.cz
tel: +420241062604

Laboratory of Odontogenesis

Head: Renata Peterkova, M.D, Ph.D.
Email: repete@biomed.cas.cz
tel: +420241062232

Scientists:

Zbynek Likovsky, Ph.D.
Renata Peterkova, M.D., Ph.D.
Maria Hovorakova, Ph.D.

Ph.D. Students:

Tomas Boran, M.D.
Tereza Krausova, M.Sc.
Barbora Nesporova, M.Sc.
Jan Prochazka, M.Sc.

Undergraduate student:

Michaela Rothova, B.Sc.
Svatava Churava, M.Sc.

Technical Assistants:

Bronislava Rokytova
Ivana Koppova
Zdena Markova

Orofacial clefts and other developmental defects - experimental and clinical aspects

Only a small part of inborn defects in man is explained either by prenatal exposure to a harmful external factor (15% of cases) or by genetic reasons (20% of cases). Most developmental defects (65%) are thought to result from prenatal exposure to the combined effect of several sub-threshold doses of external factors that act either simultaneously or sequentially; a genetic predisposition is presumed in some of these cases. We are searching for harmful external factors and genetic predisposition in clinical and epidemiological studies of inborn defects. The testing of the effect of embryotoxic factors are performed in experimental studies on animal model (chick embryogenesis) with aim of contributing to knowledge on normal and abnormal development and on the ethiopathogenesis of developmental defects.

Present studies:

• Estimation of minimum embryotoxic doses for harmful chemical and physical factors using a chick embryotoxicity screening test;
• Mechanism of development of the cleft beak in chick embryos and its possible prevention and reparation; (Fig. 1).
• Epidemiological study focused on the incidence of orofacial clefts in the Czech Republic; (Fig.2).
• Clinical study performing critical analysis of anamnesis data from parents of a child with an orofacial cleft; 
• Evaluation of orofacial growth (using x-ray and anthropometry) in patients with orofacial developmental disturbances to assess the effectiveness of surgical and orthodontic procedures;
• Monitoring of a newborn sex ratio as a tool for detection of ecological accidents.

Our studies bring new data about ethiopathogenesis of developmental defects that help in prevention of developmental anomalies in human.

Tooth development under normal, pathological and experimental conditions

Studies on tooth development (odontogenesis) studies help in understanding of molecular control of organogenesis, origin of tooth anomalies, and evolution of animal species. Since recently, odontogenesis studies also focus to making of living tooth implants, which also allows testing general principles of biotechnology of organ replacements. Experimental model in tooth developmental studies is developing mouse dentition. Our former research has brought new data on mouse odontogenesis: during early development, mouse dentition comprises also ancestral rudimental (vestigial) tooth primordia; these primordia are either incorporated into developing functional teeth, or suppressed by epithelial apoptosis; the supernumerary teeth in mouse mutants have been interpreted as atavisms based on revival of rudimental tooth anlagen. These data bring new aspects on the molecular control of odontogenesis and on evolution of dentition in mammals.

Present studies:

• Development of dentition and adjacent oral structures in human; (Fig. 3, 4).
• Odontogenesis in wild type mice - model of normal development of mammalian dentition;
• Comparative odontogenesis studies;
• Development of tooth anomalies in mice with gene disturbances (mutant, transgenic or knock-out mice); (Fig. 5).
• Experimental odontogenesis studies (role of growth activating or inhibiting factors)

Our studies will bring data about role of rudimental tooth primordia during development of mammalian dentition and about possibilities of their experimental revival. They will help in elucidating origin of tooth defects and developing technology of tooth replacement in human.

Explanation of figures

Fig. 1. Orofacial cleft in an experimental model.

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(A) The injection of a test substance into the amniotic sac of the chick embryo in ovo. (B) Unilateral cleft beak in day 9 chick embryo after the intra-amniotic injection of hydrocortisone on day 4 of incubation

Fig. 2. Orofacial clefts in man.

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(A) The mean incidence of orofacial clefts in the districts of the Czech Republic during 1983-1997. (B) Basic types of orofacial clefts in man. CL – cleft lip on the left side, CLP – cleft lip and palate on the left side, CP – isolated cleft palate, N – control

Fig. 3. Origin of the double upper lateral incisor in human.

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(A) Scheme of the embryonic human face with unilateral left-sided cleft of lip and jaw (green arrow). The medial nasal (mn) and the maxillary (mx) facial processes are fused on the right and not fused on the left side. ln - lateral nasal process, md – mandibular process. (B) Scheme of the human upper jaw arch viewed from the oral cavity. At the right site, the mn (red) and mx (yellow) fuse. At this place, the lateral deciduous incisor (i2) develops (dotted line), containing material from both facial processes. On the cleft (left) side, non-fusion of the mn and mx results in the jaw cleft, and consequently in the non-fusion of the dental epithelia and the formation of two i2. (C) Double deciduous lateral incisors i2 (arrow) in a patient with a left-sided alveolar cleft after surgical treatment (from the archive of the Clinic of Plastic Surgery, Prague). The midline is shaded. Deciduous central incisor (i1), deciduous canine (c).

Fig. 4. Developmental relationship between the deciduous dentition and vestibulum oris in the upper jaw of human embryos.

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(A) According to embryological textbooks, the deciduous dentition and oral vestibule take origin from the dental lamina (DL) and vestibular lamina (VL), respectively. (B) Summarization of our 2D and 3D morphological data on human embryos during prenatal week 7-8 document that no continuous vestibular lamina exists. At its place, a series of discontinuous structures (blue) transiently occur. Some of them fuse with the dental lamina (red). (C) Computer-aided 3D reconstruction of the dental and vestibular epithelium in human embryo at prenatal week 8 (posterior view).

Fig. 5. Lower cheek teeth in mutant tabby (EDA) mice with hypohidrotic ectodermal dysplasia – a syndrome homologous to a serious genetic disease in man.

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In comparison to the wild type (WT) animals, the mutant dentition shows a high variability. Lower cheek teeth in (A) adult mice and (B) day 15.5 mouse fetuses. We have classified the variable tabby dentitions in five phenotypes (Ia, Ib, Ic, IIa and IIb). M1, M2 and M3 – the first, second and third lower molar, respectively. T1, T2 and T3 – the first, second and third lower cheek tooth in mutants, respectively. Arrowheads - abortive tooth primordia suppressed by apoptosis. The different tabby phenotypes result from a defect in the segmentation of dental epithelium. At the place of one long M1 in WT (dashed lines), two smaller teeth develop in mutants. (C) A hypothetic scheme of the defect in segmentation of dental epithelium.

Name of the grant	Grant agency	Number of the grant	Principal investigator	Duration of the grant
Origin of tooth anomalies in mice with gene defects	GAČR	304/05/2665	Dr. Peterkova	2005-07
Orofacial clefts and tooth anomalies – experimental and clinical aspects	MŠMT ČR	OC B23.002	Dr. Peterka	2003-07
Non-contact 3D morphometry of the palate and face in patients with clefts	GAČR	304/05/0422	Dr. Šmahel	2005-07
Developmental anomalies of dentition in phylogenetic context	GAČR	304/07/0223	Dr. Peterkova	2007-11

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