DELAYED RETRACTION OF FILOPODIA IN GELSOLIN NULL MICE

Growth cones extend dynamic protrusions called filopodia and lamellipo dia as exploratory probes that signal the direction of neurite growth. Gelsolin, as an actin filament-severing protein, may serve an importa nt role in the rapid shape changes associated with growth cone structu res. In wild-type (wt) hippocampal neurons, antibodies against gelsoli n labeled the neurite shaft and growth cone. The behavior of filopodia in cultured hippocampal neurons from embryonic day 17 wt and gelsolin null (Gsn(-)) mice (Witke, W., A.H. Sharpe, J.H. Hartwig, T. Azuma, T .P. Stossel, and D.J. Kwiatkowski. 1995. Cell. 81:41-51.) was recorded with time-lapse video microscopy. The number of filopodia along the n eurites was significantly greater in Gsn(-) mice and gave the neurites a studded appearance. Dynamic studies suggested that most of these fi lopodia were formed from the region of the growth cone and remained as protrusions from the newly consolidated shaft after the growth cone a dvanced. Histories of individual filopodia in Gsn(-) mice revealed elo ngation rates that did not differ from controls but an impaired retrac tion phase that probably accounted for the increased number of filopod ia long the neutrite shaft. Gelsolin appears to function in the initia tion of filopodial retraction and in its smooth progression.