The craniofacial features endow vertebrates with unparalleled evolutionary advantages. The craniofacial is composed of bone, cartilage, nerves, and connective tissues mainly developed from cranial neural crest cells (cNCCs). These tissues form complex organs which enable vertebrates to have powerful neural and sensory systems. NCCs are groups of migratory and pluripotent cells that are specific to vertebrates. The specification, premigration and migration, proliferation, and fate determination of the NCCs are precisely and sequentially controlled by gene regulatory networks, to ensure the ordered and accurate development of the craniofacial region. The craniofacial region represents a combined set of highly heritable phenotypes, which could be illustrated by the inherited facial features between relatives but perceptible differences among non-relatives. Such phenomena are termed heredity and variation, which are in accordance with the precision and plasticity of cNCCs gene regulatory network, respectively. Evidence has shown that genetic variations within the regulatory network alter the proliferation and differentiation of NCCs within a tolerable range, while deleterious mutations will lead to craniofacial malformations. In this review, we first summarize the development procedure of NCCs and their gene regulatory networks and then provide an overview on the genetic basis of the facial morphology and malformations. This review will benefit the understanding of craniofacial development and the prevention of craniofacial diseases.
颅面部赋予脊椎动物无与伦比的进化优势，其由颅神经嵴细胞发育而来的骨、软骨、神经、肌肉等组织组成，使脊椎动物具备了复杂的神经和感官系统。神经嵴细胞是脊椎动物特有的具备迁移性、多能性的细胞类群，它们在增殖、迁移、分化过程中受到多个基因网络的时序调控，从而参与复杂颅面部的形成。同时，颅面部又是一组高度可遗传的表型组合，并具有两个特征：在亲缘后代中的可遗传性及在不同个体间的高度可变性，这两个特征分别提示了颅神经嵴细胞发育调控网络的精准性和可塑性。调控网络内基因适度突变会改变颅神经嵴细胞的增殖和分化从而产生表型可塑性，而有害的遗传突变则将导致畸形产生。本文梳理了对颅面部发育起决定作用的神经嵴细胞的发育过程及基因调控网络，在遗传层面总结了已知的颅面部表型多样性的决定基础和颅面畸形的致病机制，以期为了解颅面部发育过程以及为颅面疾病的防控提供全面认知。.
Keywords: cranial neural crest cells; craniofacial development; gene regulatory network; genetic variation.