Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs

Abstract

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 morphogesesis, 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.