Young D L, Schneider R A, Hu D, Helms J A
Department of Orthopaedic Surgery, School of Medicine, University of California at San Francisco, 94143-0514, USA.
Crit Rev Oral Biol Med. 2000;11(3):304-17. doi: 10.1177/10454411000110030201.
Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as Sonic hedgehog (Shh), epidermal growth factor receptor (EGFR), Distal-less (Dlx), and transforming growth factor beta 3 (TGFbeta3). We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face.
颅面畸形是人类最常见的出生缺陷，其中面部裂隙占这些缺陷的大部分。由于改变细胞外基质以及影响细胞的模式形成、迁移、增殖和分化的干扰因素，面部裂隙可在发育的任何阶段出现。在本综述中，我们通过分析基因敲除实验以及鸡和小鼠致畸剂处理的影响，重点关注对面部裂隙发育基础理解的最新进展。具体而言，我们分析了对诸如音猬因子（Shh）、表皮生长因子受体（EGFR）、远端缺失（Dlx）和转化生长因子β3（TGFbeta3）等基因的敲除结果。我们还描述了诸如视黄酸、介芬胺和环杷明等致畸剂对面部裂隙的影响，并讨论了它们的作用机制。除了深入了解颅面生长异常的基础外，基因和致畸技术是理解生成面部并使其形成模式的正常发育过程的有力工具。
