The function of Bmps and Runx2 in normal tooth development and in the pathogenesis of cleidocranial dysplasia

The development of many embryonic organs is regulated by reciprocal and sequential epithelial-mesenchymal interactions. These interactions are mediated by conserved signaling pathways that are reiteratively used. Cleidocranial dysplasia (CCD) is a congenital syndrome where both bone and tooth development is affected. The syndrome is characterized by short stature, abnormal clavicles, general bone dysplasia, and supernumerary teeth. CCD is caused by mutations in RUNX2, a transcription factor that is a key regulator of osteoblast differentiation and bone formation. The first aim of this study was to analyse the expression of a family of key signal molecules, Bone morphogenetic protein (Bmp) at different stages of tooth development. Bmps have a variety of functions and they were originally discovered as signals inducing ectopic bone formation. We performed a comparative in situ hybridisation analysis of the mRNA expression of Bmp2-7 from initiation of tooth development to differentiation of dental hard tissues. The expression patterns indicated that the Bmps signal between the epithelial and mesenchymal tissues during initiation and morphogenesis of tooth development, as well as during the differentiation of odontoblasts and ameloblasts. Furthermore, they are also part of the signalling networks whereby the enamel knot regulates the patterning of tooth cusps. The second aim was to study the role of Runx2 during tooth development and thereby to gain better understanding of the pathogenesis of the tooth phenotype in CCD. We analysed the tooth phenotype of Runx2 knockout mice and examined the patterns and regulation of Runx2 gene expression.. The teeth of wild-type and Runx2 mutant mice were compared by several methods including in situ hybridisation, tissue culture, bead implantation experiments, and epithelial-mesenchymal recombination studies. Phenotypic analysis of Runx2 -/- mutant tooth development showed that teeth failed to advance beyond the bud stage. Runx2 expression was restricted to dental mesenchyme between the bud and early bell stages of tooth development and it was regulated by epithelial signals, in particular Fgfs. We searched for downstream targets of Runx2 by comparative in situ hybridisation analysis. The expression of Fgf3 was downregulated in the mesenchyme of Runx2 -/- teeth. Shh expression was absent from the enamel knot in the lower molars of Runx2 -/- and reduced in the upper molars. In conclusion, these studies showed that Runx2 regulates key epithelial-mesenchymal interactions that control advancing tooth morphogenesis and histodifferentiation of the epithelial enamel organ. In addition, in the upper molars of Runx2 mutants extra buddings occured at the palatal side of the tooth bud. We suggest that Runx2 acts as an inhibitor of successional tooth formation by preventing advancing development of the buds. Accordingly, we propose that RUNX2 haploinsuffiency in humans causes incomplete inhibition of successional tooth formation and as a result supernumerary teeth.

"Kyl mä varmaan kohta ymmärrän." : Asunnon suunnittelu -opetusohjelma oppilaiden ajattelun ja oppimisen haastajana peruskoulun kotitalousopetuksessa

"I will soon understand." The House Planning Program as an Enhancer of Pupils´ Thinking Skills and Learning in Home Economics at Comprehensive School The aim of the research was to build a study program for home economics education in order to enhance pupils´ thinking skills. The program was based on the intervention programs or strategies known as Cognitive Acceleration (CA), which are founded on the theories of Jean Piaget, Lev Vygotsky, and Reuven Feuerstein. In addition, Carl Bereiter s theory of knowledge building was integrated to the research. The viewpoint of home economics was based on the multidimensional foundation of home economics science, particularly household technology and house planning. I first analyzed the kind of body of knowledge home economics science and home economics education provides for enhancing thinking skills in home economics. For the study, a CATE (Cognitive Acceleration through Technology Education) program was adapted and modified and a House Planning program was created for home economics classes. The house planning program consisted of five lessons during which pupils learned how to make functional floor plans as well as choose furniture, household appliances and materials for the home. In order to obtain the required data, various classroom experiments were arranged in 2005 with grade 9 pupils at a comprehensive school in Helsinki. All the experiments were videotaped, and five hours of the videotaped material was edited and transcribed for closer examination. The material consisted of all the video-recorded activity of the selected study group. Interaction study and content analysis were used to analyze the data. Following the experiments, a small survey was conducted to solicit pupils´ and teacher´s opinions of the program. The analysis sheds light on the nature of pupils´ interaction and knowledge building in small group activity. Special attention was given to tracking pupils´ interaction during the socalled construction zone activity. The models and qualities of teacher´s aid and support during the lessons were examined as well. The results revealed the versatility of the pupils social interaction and common knowledge building that occurred during the small group activity. The pupils discussions, including their arguments, their sharing of ideas, and the multiple perspectives that emerged reflected home economics knowledge building. The construction zone activity appeared through expressions of cognitive conflict and metacognition. Cognitive conflict was evident in the pupils´ words and involved questioning, doubting and disputing. The metacognitive activity emerged by thinking aloud, choosing the strategies, and negotiating the results. The pupils also coordinated their activity, allocated the responsibility, and systematized their work. The teacher assisted by preparing new themes for the pupils and by participating in the small group work. The teacher´s help during the small group sessions strengthened the pupils activity in the construction zone. The results showed that one can utilize the wide multidisciplinary basis of home economics, which includes scientific knowledge but also the knowledge derived from practical activity and experience. In this study practical activity was undertaken as a planning project the result of which was a plan or a new vision for the house planning situation. The study showed that the House Planning program was able to enhance the pupils´ social interaction and collaboration. The learning environment challenged the pupils in a way that could be a gateway to further developing their thinking skills. The method of analysis created in the study could be a potential tool for examining social interaction, construction zone activity, and knowledge building in other learning environments as well. Key words: home economics, house planning, classroom experiment, thinking skills,cognitive conflict, metacognition, social interaction, knowledge building