Vector-free gravity disrupts synapse formation in cell culture

Abstract

Terrestrial organisms evolved under and are subjected to the constancy of gravity. The organisms having adapted to this environmental factor, it is possible that embryonic development may be modified by exposure to altered gravity. To test the effects of gravity on embryonic development, we monitored the formation of nerve-associated acetylcholine receptor patches (NARPs) as an index of synaptogenesis. Embryonic spinal neuron and myotomal myocyte cocultures were placed in a horizontally rotating clinostat. From the cell's perspective, this results in the cancellation of the gravitational vector because of continuous averaging, thus mimicking the reduced gravitational force encountered in space. NARPs from cultures in which nerve-muscle contact was established before the onset of rotation were unaffected. In contrast, cultures in which nerve contact took place during rotation showed a marked inhibition of NARPs. Moreover, in the myocytes which did exhibit NARPs, the area of the patch was significantly reduced compared with control sister cultures. Several paradigms were used to ascertain that these findings did not result simply from loss of contact between neurites and myocytes, accelerated diffusion of a putative aggregating factor secreted by neurites, or from turbulence in the medium. Our data suggest that the process of synapse formation is sensitive to the gravitational vector. Embryonic development of the nervous system, in space, may therefore be markedly different from that normally occurring on earth.