Deviations from the precisely coordinated programme of human head development can lead to craniofacial and orofacial malformations often including a variety of dental abnormalities too. Although the aetiology is still unknown in many cases, during the last decades different intracellular signalling pathways have been genetically linked to specific disorders. Among these pathways, the RAS/extracellular signal-regulated kinase (ERK) signalling cascade is the focus of this review since it encompasses a large group of genes that when mutated cause some of the most common and severe developmental anomalies in humans. We present the components of the RAS/ERK pathway implicated in craniofacial and orodental disorders through a series of human and animal studies. We attempt to unravel the specific molecular targets downstream of ERK that act on particular cell types and regulate key steps in the associated developmental processes. Finally we point to ambiguities in our current knowledge that need to be clarified before RAS/ERK-targeting therapeutic approaches can be implemented.

中文翻译：

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颅面、口面和牙齿疾病：RAS/ERK 通路的作用

偏离人类头部发育的精确协调计划会导致颅面和口面畸形，通常也包括各种牙齿异常。尽管在许多情况下病因仍然未知，但在过去的几十年中，不同的细胞内信号通路在遗传上与特定疾病有关。在这些通路中，RAS/细胞外信号调节激酶 (ERK) 信号级联是本综述的重点，因为它包含一大组基因，这些基因在发生突变时会导致人类一些最常见和最严重的发育异常。我们通过一系列人类和动物研究展示了与颅面和口腔疾病有关的 RAS/ERK 通路的成分。我们试图解开 ERK 下游作用于特定细胞类型并调节相关发育过程中的关键步骤的特定分子靶点。最后，我们指出了在我们目前的知识中需要澄清的模糊性，然后才能实施 RAS/ERK 靶向治疗方法。