Организация, в которой проходила защита:
Department of Pharmacology and Physiology, Karolinska Institutet, Stockholm, Sweden
Год защиты:2016
Аннотация:Development of the head and face involves growth of the tissues, a vast number of cell interactions and tightly controlled gene expressions to generate functioning tissue or organ. Numbers of diseases or traumas such as cleft lip and palate or loss of teeth are difficult to treat because of the face complexity. Understanding development is a crucial basis for regenerative medicine. To study patterns of cellular movements during tooth development we used transgenic mice embryos of embryonic day 16 and 17.5 (E16, E17.5). Mice have evolved from the common ancestor as humans thus it makes a good research model. Here we study how the tooth is developing and growing by estimating two mechanisms: the cell division rates and oriented daughter cell divisions in the dental pulp. The cell division rates and direction were analysed using transgenic mice (traced from E14) that express green fluorescent protein (GFP) in nucleus creating the gradient of GFP. Additionally, the daughter cells division directions were tackled using a different mouse strain (traced from E8.5) that included a construct in their genome allowing expression of four fluorescent proteins: green, yellow, cyan and red. By combining these methods we observed that tooth shaping results from oriented cell divisions in dental compartment that are aligned at certain possible angles between cell division direction and tooth elongation during tooth organogenesis. Our results indicated that mostly the cell aligns its clones at about 20 degrees' angle. The cell division rate is greatest at the top of the forming tooth, the least dividing cells at the base and the intermediate zone is in between. We can conclude that oriented daughter cells' divisions and movement depends on a polarizing signals, one of them-protein Wnt5a, coming from the direction of an enamel organ; the stronger the signal, the more cells divide. These cellular mechanisms propose the strategy behind tooth development and shaping suggesting the tissue polarity principle of cell division gradient and migration directions in a developing tooth.