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Head: Assoc. Prof. Miroslav Peterka, MD, DSc

Phone: +420 241 062 604
The main focuses of the Department of Teratology are studies on developmental abnormalities in humans as well as in experime- ntal models. The causes and mechanisms of the inborn defect formation are studied using two experimental models (developing chick embryo and mouse odontogenesis), and using a clinical- epidemiological approach. The main target is to contribute to the knowledge about normal and abnormal development, pathogene- sis of inborn defects and possibilities of their prevention.

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Laboratory of Embryogenesis

Assoc. Prof. Miroslav Peterka, MD, DSc | Head of Laboratory
Phone: +420 241 062 604

Laboratory of Odontogenesis

Renata Peterková, MD, PhD | Head of Laboratory
Phone: +420 241 062 232
Miroslav Peterka, MD, DSc | Research Scientist

 

Zuzana Pavlíková, MSc | PhD Student

 

Petra Herlová, MSc | Technician
Simona Vojtěchová, MSc | Technician
Šárka Dvořáková | Technician

 

Renata Peterková, MD, PhD | Research Scientist
Mária Hovořáková, MSc, PhD | Research Scientist
Oldřich Zahradníček, MSc, PhD | Research Scientist
Svatava Lagronová, MSc, PhD | Research Scientist

 

Lucie Horáková, MSc | PhD Student
Kateřina Lochovská, MSc | PhD Student

Klára Steklíková | PhD Student

 

Ivana Koppová | Technician
Zdena Lisá | Technician
Lenka Jandová | Technician

Linda Dalecká | Technician

Laboratory of Embryogenesis

 

In clinical-epidemiological studies, we are monitoring the incidence of orofacial clefts in the Czech population,and searching for possible causes of cleft origin using anamnestic data. Suspected inducing harmful factors, mainly the drugs used during pregnancy, are then tested experimentally. The testing of embryotoxicity is made on chick embryos using the chick embryotoxicity screening test (CHEST ) method. The results of the testing are evaluated on the basis of occurrence of lethal effect, growth retardation and developmental malformations in the chick embryos.

 

Laboratory of Odontogenesis

 
The Laboratory is focused on the studies of tooth development under normal, pathological and experimental conditions. We have discovered that rudimen- tary tooth primordia play an important role during mouse odontogenesis. Although the rudiments disappear later prenatally, a defect in their formation can be involved in the origin of tooth anomalies. Elucidation of development and role of the rudimentary structures during odontogenesis can contribute to better understanding of tooth evolution as well as the origin of tooth ano- malies. For example, an unsuppressed (revitalised) rudiment, which continues in development, can give rise to a supernumerary tooth. In this respect, such regressing or revitalising rudiments represent a natural model to study the mechanisms inhibiting or stimulating tooth development, and for testing possibilities of tooth regeneration. 
 

Important result in 2015

 

Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation.

In normal mice, the signalling centres of a premolar rudimentary bud and the first molar anlage fuse together to commonly form one typical signalling centre (primary enamel knot) of the first molar. With decreasing Sprouty2 and Sprouty4 gene dosages, we observed a non-fusion of the above mentioned signalling centres, with consequent formation of a supernumerary tooth primordium from the individually developing premolar bud. Our findings significantly contribute to existing knowledge about supernumerary tooth formation.

 

 

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Fig 1: Development of a supernumerary tooth in mouse embryos.

 

References:

Lochovska K, Peterkova R, Pavlikova Z, Hovorakova M. Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation. BMC Dev Biol. 2015 Apr 22;15:21. doi: 10.1186/s12861-015-0070-0

 

 

Important result in 2014

 

Three-dimensional analysis of the early development of the dentition
The present reviews survey data provided by 20 years research of odontogenesis in the laboratory mouse and in humans. Our results disprove the generally accepted concept of dentition morphogenesis, and offer new interpretations of results of studies on interactions between dental epithelium and mesenchyme, and on molecular control of tooth development in the mouse model. Such knowledge is important for future methods aimed to development of tooth biological replacements, when a tooth implant resulting from controlled differentiation of living cells will be anchored to a jaw.
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Fig. 1. Summarized data on developing dentition and oral vestibule in human and their tentative comparison with developing teeth in fishes. (A) Embryological textbooks present two parallel U-shaped ridges in human embryos: DL - dental lamina (giving rise to the deciduous dentition) and VL - vestibular lamina or labio-gingival band (where oral vestibule will form). (B) Summarization of our data by 3D reconstructions document no continuous vestibular lamina exists. Instead, a set of discontinuous epithelial structures (ridges and bulges) transiently occurs externally to the dental epithelium. Red - dental epithelium. Yellow or blue – vestibular epithelium. c, m1, m2 – the deciduous canine, first and second molar, respectively. AC – the accessory cap-shaped structure. (D) The schematic pattern of tooth rows (“Zahnreihen”) in fishes. The empty rings and black spots indicate the older and younger teeth, respectively, new teeth are formed at the posterior end of each Zahnreihen. (E) Dental and vestibular epithelium in 8 weeks old human embryonic maxilla in a 3D reconstruction viewed from mesenchymal aspect. Note the reiterative fusions (white asterisks) between the dental epithelium and particular ridges of the vestibular epithelium. c, m1 – the deciduous canine and the first molar, respectively.

 

 

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Fig. 2. Correlation between Shh signaling centers and developing teeth in the mandible of WT mice. Insert: Shh in situ hybridization of the whole mandible at embryonic day 12.5. Rectangles – functional teeth; round and oval shapes – Shh expression domains of developing teeth. Classical view: According to the literature, Shh expression is present in two signaling centers in each mandible half. The anterior one corresponds to the incisor primordium (I), the posterior one corresponds to the first molar (M1) until embryonic day 14. New view: According to the summary of our recent results, the Shh expression appears in several domains along the antero-posterior jaw axes of the lower jaw. The earlier-appearing domains correspond to the rudimentary tooth primordia in the incisor (pt-green) and cheek (MS-blue; R2-red) regions. Later, the primordia of functional teeth with their signaling centers appear: incisor (I-yellow), first molar (M1-yellow). The signaling centers MS, R2 and M1 appear successively in the distal direction. In adults, the functional M1 takes its origin with the contribution of R2 rudiment (red rectangle). A minor contribution of MS rudiment cannot be excluded (blue rectangle).

 

Collaboration: Lesot Hervé, Institut National de la Sante et de la Recherche Medicale, UMR 1109, Team ‘Osteoarticular and Dental Regenerative NanoMedicine’, Strasbourg, France

 
References:

Peterkova R, Hovorakova M, Peterka M, Lesot H. Three-dimensional analysis of the early development of the dentition. Aust Dent J. 2014, 59 Suppl 1:55-80. IF:1.482

Lesot H, Hovorakova M, Peterka M, Peterkova R. Three-dimensional analysis of molar development in the mouse from the cap to bell stage. Aust Dent J. 2014, 59 Suppl 1:81-100. IF: 1.482 

 

Important result in 2013

 

The Reinterpretation of the data on Shh signaling during the early development of the mouse dentition
The tooth development in mice is one of the most often used models to study regulation mechanisms of organogenesis. Since recently, this model started to be used to develop methods of tooth engineering and regeneration. Correct interpretation of the morphological and molecular data is an essential prerequisite of the reliable conclusions of developmental studies on the mouse model of odontogenesis.
We have shown in our study that the firstly appearing structures and its corresponding Shh expression in the upper incisor region in mice (Fig. 1) are not related to two functional incisors but to the tooth rudiments suppressed during evolution (Hovorakova et al., 2013).
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Fig. 1. The early development in the prospective incisor region in the mouse.
(A) Two generations of the Shh expression domains (green and yellow, respectively) and their sequential development are documented on the hybridized upper jaws (B–D), and corresponding 3D reconstructions of the dental and adjacent oral epithelium with visualized Shh expression domains (red), (E–G). Two generations of Shh expression domains correspond to two generations of tooth primordia. The first generation (green arrow) appears anteriorly and it corresponds to the rudimentary primordium. The second generation (yellow arrow) appears posteriorly and it corresponds to the signaling center of the functional incisor.

 

 

The upper mouse incisor development study has finished our systematic revision of classical data on mouse model of tooth development published in the most recent paper by Peterkova et al. (2014). We have shown in both the incisor and cheek region of a jaw that the development until ED13 corresponds to the rudimentary tooth primordia suppressed during evolution. This is in contrast to the classical view assuming their correspondence to the functional teeth. However, the primordia of functional teeth appear later (Fig. 2).

The developing dentition of mice contains primordia, with progressive or regressive development. The studies on their development allow determination of regulation factors involved in growth stimulation or growth retardation. Such information can be very important for regenerative medicine. 

 

 

References:

Hovorakova M, Smrckova L, Lesot H, Lochovska K, Peterka M, Peterkova R. Sequential Shh expression in the development of the mouse upper functional incisor. J Exp Zool B Mol Dev Evol. 320B: 455–464, 2013. IF 2,123