Cole Francesca, Krauss Robert S
Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Curr Biol. 2003 Mar 4;13(5):411-5. doi: 10.1016/s0960-9822(03)00088-5.
Holoprosencephaly (HPE), the most common developmental defect of the forebrain and midface, is caused by a failure to delineate the midline in these structures. Despite the identification of several HPE genes, its genetic basis is largely unknown. Furthermore, the phenotype of affected individuals is highly variable, even within pedigrees. Facial defects in HPE range from cyclopia and proboscis in severe cases to solitary median maxillary central incisor in individuals with microforms of HPE. Cdon (also known as Cdo), an Ig superfamily member, is a component of a cell surface receptor that positively regulates skeletal myogenesis. Cdon is also highly expressed in the frontonasal and maxillary processes (FNP and MXP, respectively) of the developing mouse embryo, structures that contain signaling centers that pattern the face. We report here that mice homozygous for targeted mutations of Cdon display the hallmark facial defects associated with microforms of HPE. This is the first example of a mouse mutant with this phenotype, and this finding implicates a new family of receptors in development of the facial midline and suggests a potential role for Cdon in the pathogenesis and expressivity of HPE in humans.
前脑无裂畸形（HPE）是最常见的前脑和中面部发育缺陷，由这些结构中线的划分失败所致。尽管已鉴定出多个HPE基因，但其遗传基础仍大多未知。此外，即使在同一家系中，受影响个体的表型也高度可变。HPE中的面部缺陷范围从严重病例中的独眼畸形和鼻状物到HPE微小型个体中的孤立性上颌中切牙。Cdon（也称为Cdo）是免疫球蛋白超家族成员，是一种细胞表面受体的组成部分，可正向调节骨骼肌生成。Cdon在发育中的小鼠胚胎的额鼻突和上颌突（分别为FNP和MXP）中也高度表达，这些结构包含对面部进行模式化的信号中心。我们在此报告，Cdon靶向突变的纯合小鼠表现出与HPE微小型相关的标志性面部缺陷。这是具有该表型的小鼠突变体的首个实例，这一发现表明一个新的受体家族参与面部中线的发育，并提示Cdon在人类HPE的发病机制和表现度中可能发挥作用。
