Control of Axonal Sprouting and Dendrite Branching by the Nrg-Ank Complex at the Neuron-Glia Interface

Abstract

Neurons are highly polarized cells with distinct subcellular compartments, including dendritic arbors and an axon. The proper function of the nervous system relies not only on correct targeting of axons, but also on development of neuronal-class-specific geometry of dendritic arbors [1-4]. To study the intercellular control of the shaping of dendritic trees in vivo, we searched for cell-surface proteins expressed by Drosophila dendritic arborization (da) neurons [5-7]. One of them was Neuroglian (Nrg), a member of the Ig superfamily ; Nrg and vertebrate L1-family molecules have been implicated in various aspects of neuronal wiring, such as axon guidance, axonal myelination, and synapse formation [9-12]. A subset of the da neurons in nrg mutant embryos exhibited deformed dendritic arbors and abnormal axonal sprouting. Our functional analysis in a cell-type-selective manner strongly suggested that those da neurons employed Nrg to interact with the peripheral glia for suppressing axonal sprouting and for forming second-order dendritic branches. At least for the former role, Nrg functioned in concert with the intracellular adaptor protein Ankyrin (Ank) [13]. Thus, the neuron-glia interaction that is mediated by Nrg, together with Ank under some situations, contributes to axonal and dendritic morphogenesis.

unc-44 Ankyrin and stn-2 γ-Syntrophin Regulate sax-7 L1CAM Function in Maintaining Neuronal Positioning in Caenorhabditis elegans

“…An alternative mechanism by which UNC-44 regulates SAX-7 function may be in controlling SAX-7 localization. Previous studies show that ankyrin is required to maintain L1 in some axon tracts in the mouse and, more recently, in Drosophila (Scotland et al 1998;Yamamoto et al 2006). However, our data do not support this idea.…”

“…Previous analyses in the mouse and Drosophila revealed that ankyrin mutants exhibit phenotypes similar to the respective mouse L1 and Drosophila neuroglian mutants, suggesting that both ankyrin and L1CAM function in the same process (Scotland et al 1998;Yamamoto et al 2006). Together with data showing that UNC-44 binds SAX-7, we hypothesize that a mechanism by which UNC-44 regulates SAX-7 function may be in providing SAX-7 anchorage to the spectrin-actin cytoskeleton, thereby increasing SAX-7-mediated adhesion.…”

Deletion of the mouse RegIIIβ (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons

“…We found that there were no differences between the two groups (wild type: lateral, 352.3 Ϯ 25.8; medial, 980.3 Ϯ 9.5; KO: lateral, 360.0 Ϯ 16.5; medial, 950.3 Ϯ 41.9 KO; n ϭ 3 in each group). We concluded that excess collateralization of hypoglossal axons occurs because of delayed myelination during the early postnatal period in KO mice and is lost later by selective pruning of excess axonal branches (22,23).…”

spineless provides a little backbone for dendritic morphogenesis: Figure 1.

“…Drosophila da dendrite morphogenesis can be divided into two components: an intrinsic program establishing a basic dendritic pattern, and an extrinsic program influenced by support cells (Yamamoto et al 2006) and competition between dendrites from similar neurons (Grueber and Jan 2004). The phenotypic analyses of a rapidly expanding number of genes that influence dendrite morphogenesis provide evidence that the intrinsic program can be further subdivided into genes that control discrete aspects of dendrite formation.…”