Neurobiology Select

This issue's Neurobiology Select highlights different molecular aspects of the patterning of neuronal circuits during development, as well as factors that determine the number of neurons in the circuit. The network of neu-ronal dendrites receives synaptic input often through specialized structures called spines, and we highlight some recent insights into how these structures are formed. We also describe studies that identify factors that contribute to synapse number and brain size. During development of the mammalian central nervous system, many connections are forged and then broken in the process of establishing the correct neuronal circuits. How a neuron makes the right connections during development depends on the correct patterning of both its axons and its dendrites. Dendrites form distinct branching networks that resemble a tree (arbor) and some dendritic arbors have specialized, morphologically distinct protrusions called spines. Neuronal activity is often the factor that determines which neural connections are retained and which are not. But how does neuronal activity correlate with changes in dendritic patterning during development? To study this question, But-tery et al. focused on the a1-chimaerin protein, which is upregulated during neuronal development when synapses are being formed. In this study, the authors show that overexpression of a1-chimaerin in mouse cerebellar Purkinje cells and hippocampal neurons caused a reduction in the number of dendritic spines, as well as a decrease in dendrite length and the number of branch points. RNAi against a1-chimaerin resulted in neurons with atypical spines that had filopodial extensions , suggesting that this protein may prune dendrites. a1-chimaerin is a GTPase activating protein (GAP) that negatively regulates the small GTPase Rac1 (which regulates actin dynamics); it also binds to the lipid diacylglycerol (DAG). In response to neuronal activity, a1-chimaerin becomes relocalized to the plasma membrane, a change that is dependent on the DAG binding domain (C1). Furthermore, blocking neuronal activation decreased expression of a1-chimaerin by more than 60% in cultured postnatal mouse hippocampal neurons. These data support a model in which signaling through lipids, stimulated by neuronal activity, leads to relocalization of a1-chimaerin to the plasma membrane. Here, a1-chimaerin inactivates Rac, thereby limiting growth of dendrites mediated by the actin cytoskeleton. As dendritic spines are highly polarized structures, Zhang and Macara (2006) examined the role of the cell polarity protein PAR-3 in their morphogenesis. They found that PAR-3 is localized to the postsynaptic membrane and that knock-down of PAR-3 by RNAi in cultured hippocampal neurons from …