Kitsukawa T, Shimono A, Kawakami A, Kondoh H, Fujisawa H
Department of Molecular Biology, School of Science, Nagoya University, Japan.
Development. 1995 Dec;121(12):4309-18. doi: 10.1242/dev.121.12.4309.
Neuropilin is a type 1 membrane protein, which is highly conserved among Xenopus frog, chicken and mouse. The extracellular part of the neuropilin protein is composed of three unique domains, each of which is thought to be involved in molecular and/or cellular interactions. In mice, neuropilin is expressed in the cardiovascular system, nervous system and limbs at particular developmental stages. To clarify the roles of neuropilin in morphogenesis in vivo, we generated mouse embryonic stem (ES) cell clones that constitutively expressed exogenous neuropilin, then produced chimeras using these ES cell clones. The chimeras overexpressed neuropilin and were embryonic lethal. The chimeric embryos exhibited several morphological abnormalities; excess capillaries and blood vessels, dilation of blood vessels, malformed hearts, ectopic sprouting and defasciculation of nerve fibers, and extra digits. All of these abnormalities occurred in the organs in which neuropilin is expressed in normal development. The variety of abnormalities occurring in these chimeric embryos suggested diverse functions of neuropilin in embryonic morphogenesis, which may be ascribed to multiple interaction domains identified in the molecule. Correct spatiotemporal expression of neuropilin seems to be essential for normal development of the cardiovascular system, nervous system and limbs.
神经纤毛蛋白是一种1型膜蛋白，在非洲爪蟾、鸡和小鼠中高度保守。神经纤毛蛋白的细胞外部分由三个独特的结构域组成，每个结构域都被认为参与分子和/或细胞相互作用。在小鼠中，神经纤毛蛋白在特定发育阶段的心血管系统、神经系统和四肢中表达。为了阐明神经纤毛蛋白在体内形态发生中的作用，我们构建了组成型表达外源性神经纤毛蛋白的小鼠胚胎干细胞（ES细胞）克隆，然后使用这些ES细胞克隆制备嵌合体。这些嵌合体过度表达神经纤毛蛋白且胚胎致死。嵌合胚胎表现出几种形态学异常；毛细血管和血管过多、血管扩张、心脏畸形、神经纤维异位发芽和脱束，以及多指。所有这些异常都发生在神经纤毛蛋白在正常发育中表达的器官中。这些嵌合胚胎中出现的各种异常表明神经纤毛蛋白在胚胎形态发生中具有多种功能，这可能归因于该分子中鉴定出的多个相互作用结构域。神经纤毛蛋白正确的时空表达似乎对心血管系统、神经系统和四肢的正常发育至关重要。
