Normal levels of Rac1 are important for dendritic but not axonal development in hippocampal neurons

Background information. Rho family GTPases are required for cytoskeletal reorganization and are considered important for the maturation of neurons. Among these proteins, Rac1 is known to play a crucial role in the regulation of actin dynamics, and a number of studies indicate the involvement of this protein in different steps of vertebrate neuronal maturation. There are two distinct Rac proteins expressed in neurons, namely the ubiquitous Rac1 and the neuron-specific Rac3. The specific functions of each of these GTPases during early neuronal development are largely unknown. Results. The combination of the knockout of Rac3 with Rac1 down-regulation by siRNA (small interfering RNA) has been used to show that down-regulation of Rac1 affects dendritic development in mouse hippocampal neurons, without affecting axons. F-actin levels are strongly decreased in neuronal growth cones following down-regulation of Rac1, and time-lapse analysis indicated that the reduction of Rac1 levels decreases growth-cone dynamics. Conclusions. These results show that normal levels of endogenous Rac1 activity are critical for early derldritic development, whereas dendritic outgrowth is not affected in hippocampal neurons from Rac3-null mice. On the other hand, early axonal development appears normal after Rac1 down-regulation. Our findings also suggest that the initial establishment of neuronal polarity is not affected by Rac1 down-regulation.