Regulation of dendritic branching by Cdc42 GAPs

Abstract

Nerve cells form elaborate, highly branched dendritic trees that are optimized for the receipt of synaptic signals. Recent work published in this issue of Genes & Development by Rosario and colleagues (pp. 1743-1757) shows that a Cdc42-specific GTPase-activating protein (NOMA-GAP) regulates the branching of dendrites by neurons in the top layers of the mouse cortex. The results raise interesting questions regarding the specification of arbors in different cortical layers and the mechanisms of dendrite branching.

Figure 1.

Dendrite development in the neocortex. (A) Development of normal and NOMA-GAP mutant cortex. Time course of development with approximate embryo ages. (E14.5 [embryonic day 14.5]) Layer 5 cells (blue) arrive below layer 1, trailing an axon (orange) behind. (E16.5) The leading processes of layer 5 cells extend as the cortex grows, with layer 4 cells (not shown) inserting between layer 5 and layer 1. Layer 2/3 cells are entering from below. (E18.5) Layer 2/3 cells (red) arrive between layer 4 and layer 1. Primary dendrites have formed layer 5 cells. (Birth) Primary dendrites have formed layer 2/3 cells. Branches forming on layer 5 cells. (P5 [postnatal day 5]) Branches forming on layer 2/3 dendrites. Dendrites continue to remodel in response to activity. (NOMA-GAP^−/−) Layer 2/3 is reduced in size because the cells have normal primary dendrites but few branches. Layer 5 cells have normal dendritic branching close to the cell body (i.e., in layer 5). The extent of branching of layer 5 cell dendrites in layer 2/3 is not known (pale blue). (B) Possible mechanisms of dendrite branching by either branching of the growth tip or stabilization of filopodia on the dendrite shaft. (*) Lamellipodia; (arrowheads) filopodia; (arrows) direction of growth. (C) Signaling pathways that regulate dendrite branching in layer 2/3. Steps established by Rosario et al. 2012 are highlighted in red.