Department of Craniofacial Development and Stem Cell Biology, King's College London, London, United Kingdom ; Department of Anatomy, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
PLoS One. 2013 Sep 3;8(9):e74484. doi: 10.1371/journal.pone.0074484. eCollection 2013.
In contrast to mammals, most reptiles constantly regenerate their teeth. In the snake, the epithelial dental lamina ends in a successional lamina, which proliferates and elongates forming multiple tooth generations, all linked by a permanent dental lamina. To investigate the mechanisms used to control the initiation of new tooth germs in an ordered sequential pattern we utilized the polyphodont (multiple-generation) corn snake (Pantherophis guttatus). We observed that the dental lamina expressed the transcription factor Sox2, a multipotent stem cell marker, whereas the successional lamina cells expressed the transcription factor Lef1, a Wnt/β-catenin pathway target gene. Activation of the Wnt/β-catenin pathway in culture increased the number of developing tooth germs, in comparison to control untreated cultures. These additional tooth germs budded off from ectopic positions along the dental lamina, rather than in an ordered sequence from the successional lamina. Wnt/β-catenin activation enhanced cell proliferation, particularly in normally non-odontogenic regions of the dental lamina, which widely expressed Lef1, restricting the Sox2 domain. This suggests an expansion of the successional lamina at the expense of the dental lamina. Activation of the Wnt/β-catenin pathway in cultured snake dental organs, therefore, led to changes in proliferation and to the molecular pattern of the dental lamina, resulting in loss of the organised emergence of tooth germs. These results suggest that epithelial compartments are critical for the arrangement of organs that develop in sequence, and highlight the role of Wnt/β-catenin signalling in such processes.
与哺乳动物不同，大多数爬行动物的牙齿可以不断再生。在蛇中，上皮性齿状嵴终末于连续嵴，该连续嵴增殖和伸长形成多个牙代，所有牙代都由一个永久性齿状嵴连接。为了研究控制新牙原基有序发生的机制，我们利用多齿（多代）玉米蛇（ Pantherophis guttatus ）进行了研究。我们观察到齿状嵴表达转录因子 Sox2，这是多能干细胞标志物，而连续嵴细胞表达转录因子 Lef1，这是 Wnt/β-catenin 途径的靶基因。与未经处理的对照培养物相比，在培养物中激活 Wnt/β-catenin 途径会增加发育中的牙原基数量。这些额外的牙原基从齿状嵴的异位位置萌出，而不是从连续嵴按顺序萌出。Wnt/β-catenin 激活增强了细胞增殖，特别是在齿状嵴中通常非成牙质区域，这些区域广泛表达 Lef1，限制了 Sox2 域。这表明连续嵴的扩展是以齿状嵴为代价的。因此，在培养的蛇齿状器官中激活 Wnt/β-catenin 途径导致增殖和齿状嵴的分子模式发生变化，导致牙原基的有序出现丧失。这些结果表明上皮细胞区室对于按顺序发育的器官的排列至关重要，并强调了 Wnt/β-catenin 信号在这些过程中的作用。
