Lysophosphatidic acid influences initial neuronal polarity establishment

Abstract

Neuronal polarity is specified by neurite determination into axons and dendrites. Its establishment requires both extrinsic signals, which regulate axon and dendrite development through repulsive or attractive actions, and intrinsic cellular mechanisms, which include rearrangement and selective transport of the cytoskeleton and localization of intracellular organelles. However, it remains unclear how extrinsic signals activate intrinsic cellular mechanisms to establish neuronal polarity. Here, we examine the effects of lysophosphatidic acid (LPA), a signaling lipid that induces cytoskeletal rearrangement in neuronal cells, on neuronal polarity establishment. In hippocampal neuronal cultures where a concentration gradient of LPA was formed, the bases of axons were located predominantly at the side distal to the LPA source. Furthermore, Golgi apparatus were also positioned distally as early as 1 h after exposure to the LPA source, suggesting that LPA signaling is involved in the initial determination of the area where an axon sprouts, and thereby the establishment of neuronal polarity.