Stathmin Expression Modulates Migratory Properties of GN-11 Neurons in Vitro

Abstract

Expression of stathmin, a microtubule-associated cytoplasmic protein, prominently localized in neuroproliferative zones and neuronal migration pathways in brain, was investigated in the GnRH neuroendocrine system in vivo and the function was analyzed using an in vitro approach. Here we present novel data demonstrating that GnRH migrating neurons in nasal regions and basal forebrain areas of mouse embryos express stathmin protein. In addition, this expression pattern is dependent on location, as GnRH neurons reaching the hypothalamus are stathmin negative. Immortalized GN-11 cells, which retain many characteristics of migrating GnRH neurons, strongly express stathmin mRNA and protein. The role of stathmin in GnRH migratory properties was evaluated using GN-11 cell line. We up-regulated [stathmin-transfected clones (STMN)+] and down-regulated (STMN-) the expression of stathmin in GN-11 cells, and we investigated changes in cell morphology and motility in vitro. Cells overexpressing stathmin assume a spindle-shaped morphology and their proliferation, as well as their motility, is higher with respect to parental cells. Furthermore, they do not aggregate and express low levels of cadherins compared with control cells. STMN- GN-11 cells are endowed with multipolar processes, and they show a decreased motility and express high levels of cadherin protein. Our findings suggest that stathmin plays a permissive role in GnRH cell motility, possibly via modulation of cadherins expression.