He Fenglei, Chen Yiping
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY, USA.
Front Oral Biol. 2012;16:81-90. doi: 10.1159/000337619. Epub 2012 Jun 25.
Wnt signaling regulates a variety of cell behaviors and represents a major pathway in development and disease. Mutations in Wnt genes and their downstream targets have been implicated in human craniofacial abnormalities, including the most prevalent birth defect, cleft lip with or without palate. Formation of the upper lip and palate is a complicated process and is composed of a series of highly coordinated steps during tissue morphogenesis, which are rigorously controlled by genetic networks. While genetic controls of lip/palate development have been extensively studied, the roles of Wnt signaling in these processes remained poorly understood. Within the cell, Wnt signaling is transduced in a β-catenin-dependent (canonical) or -independent (non-canonical) fashion. Recent studies have demonstrated that the canonical and non-canonical pathways play differential roles but both are essential in lip/palate development. Here we review these studies that have substantially advanced our knowledge by elucidating the function of Wnt signaling in upper lip formation, secondary palate development and their disease settings. These advances are important to delineate the genetic networks controlling craniofacial development and to develop personalized therapeutic strategies in related human birth defects in the future.
Wnt信号通路调控多种细胞行为，是发育和疾病中的一条主要信号通路。Wnt基因及其下游靶点的突变与人类颅面畸形有关，包括最常见的出生缺陷——唇腭裂（伴有或不伴有腭裂）。上唇和腭的形成是一个复杂的过程，由组织形态发生过程中一系列高度协调的步骤组成，这些步骤受到遗传网络的严格控制。虽然唇/腭发育的遗传调控已得到广泛研究，但Wnt信号通路在这些过程中的作用仍知之甚少。在细胞内，Wnt信号通路以β-连环蛋白依赖（经典）或非依赖（非经典）的方式进行转导。最近的研究表明，经典和非经典通路发挥着不同的作用，但在唇/腭发育中两者都是必不可少的。在此，我们综述这些研究，它们通过阐明Wnt信号通路在上唇形成、继发腭发育及其疾病背景中的功能，极大地推进了我们的认识。这些进展对于描绘控制颅面发育的遗传网络以及未来制定针对相关人类出生缺陷的个性化治疗策略具有重要意义。
