Shh signaling is essential for rugae morphogenesis in mice
Shh signaling is essential for rugae morphogenesis in mice
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DOI：
10.1007/s00418-011-0870-7
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发表时间：
2011-12-01
影响因子：
2.3
通讯作者：
Jung, Han-Sung
中科院分区：
文献类型：
--
作者：
Lee, Jong-Min;Miyazawa, Seita;Jung, Han-Sung
腭脊，或称腭褶，是在硬腭区域观察到的波纹状结构。它们存在于大多数哺乳动物物种中，但其数量和排列具有物种特异性。在小鼠的第二腭中发现了9个腭褶。以往的研究表明，腭嵴上皮Shh信号在皱褶发育过程中起着重要作用。此外，Wnt家族成员，包括LEF1，在口面形态发生中发挥功能性作用。为了探讨Shh在皱褶发育中的作用，我们利用5E1（抗Shh抗体）向小鼠胚胎的母体转移。5E1诱导的异常皱褶模式的特点是腭脊的斑点形状，而不是一个条纹。Shh和Shh相关基因Sostdc1、Lef1和Ptch1的表达模式在5E1注射后被破坏。此外，皱纹特异性细胞增殖和皱纹间特异性细胞凋亡受到抑制的Shh信号。我们推测，改变的基因表达模式和分子事件的变化所引起的抑制Shh信号可能会导致异常皱褶图案。此外，我们提出了一个由Wnt，Shh和Sostdc1信号产生的反应扩散模型。在这项研究中，我们表明，Sostdc 1，分泌的Wnt通路的抑制剂，是一个下游的目标Shh和假设的Wnt，Shh和Sostdc 1的相互作用是一个关键的机制控制腭皱的空间格局。
Palatal ridges, or rugae palatinae, are corrugated structures observed in the hard palate region. They are found in most mammalian species, but their number and arrangement are species-specific. Nine palatal rugae are found in the mouse secondary palate. Previous studies have shown that epithelial Shh signaling in the palatal ridge plays an important role during rugae development. Moreover, Wnt family members, including LEF1, play a functional role in orofacial morphogenesis. To explore the function of Shh during rugae development, we utilized the maternal transfer of 5E1 (anti-Shh antibody) to mouse embryos. 5E1 induced abnormal rugae patterning characterized by a spotted shape of palatal ridge rather than a stripe. The expression patterns of Shh and Shh-related genes, Sostdc1, Lef1 and Ptch1, were disrupted following 5E1 injection. Moreover, rugae-specific cell proliferation and inter-rugae-specific apoptosis were affected by inhibition of Shh signaling. We hypothesize that the altered gene expression patterns and the change in molecular events caused by the inhibition of Shh signaling may have induced abnormal rugae patterning. Furthermore, we propose a reaction-diffusion model generated by Wnt, Shh and Sostdc1 signaling. In this study, we show that Sostdc1, a secreted inhibitor of the Wnt pathway, is a downstream target of Shh and hypothesize that the interaction of Wnt, Shh and Sostdc1 is a pivotal mechanism controlling the spatial patterning of palatal rugae.