Academic journal article Genetics

Neural Maintenance Roles for the Matrix Receptor Dystroglycan and the Nuclear Anchorage Complex in Caenorhabditis Elegans

Academic journal article Genetics

Neural Maintenance Roles for the Matrix Receptor Dystroglycan and the Nuclear Anchorage Complex in Caenorhabditis Elegans

Article excerpt

ABSTRACT Recent studies in Caenorhabditis elegans have revealed specific neural maintenance mechanisms that protect soma and neurites against mispositioning due to displacement stresses, such as muscle contraction. We report that C. elegans dystroglycan (DG) DGN-1 functions to maintain the position of lumbar neurons during late embryonic and larval development. In the absence of DGN-1 the cell bodies of multiple lumbar neuron classes are frequently displaced anterior of their normal positions. Early but not later embryonic panneural expression of DGN-1 rescues positional maintenance, suggesting that dystroglycan is required for establishment of a critical maintenance pathway that persists throughout later developmental stages. Lumbar neural maintenance requires only a membrane-tethered N-terminal domain of DGN-1 and may involve a novel extracellular partner for dystroglycan. A genetic screen for similar lumbar maintenance mutants revealed a role for the nesprin/SYNE family protein ANC-1 as well as for the extracellular protein DIG-1, previously implicated in lumbar neuron maintenance. The involvement of ANC-1 reveals a previously unknown role for nucleus-cytoskeleton interactions in neural maintenance. Genetic analysis indicates that lumbar neuron position is maintained in late embryos by parallel DGN-1/DIG-1 and ANC-1- dependent pathways, and in larvae by separate DGN-1 and ANC-1 pathways. The effect of muscle paralysis on late embryonic- or larval-stage maintenance defects in mutants indicates that lumbar neurons are subject to both muscle contraction-dependent and contractionindependent displacement stresses, and that different maintenance pathways may protect against specific types of displacement stress.

AN emerging theme in neurobiology is the importance of systems dedicated to the maintenance of the intricate architecture of the nervous system (Benard and Hobert 2009). The locations of neuronal soma, axons, and dendrites must be maintained to ensure proper nervous system function during the addition and removal of neurons and synapses and in response to mechanical stresses associated with body growth and movement. The factors maintaining nervous system architecture are often distinct from those involved in its establishment during development, a division of labor which likely allows flexibility to cope with the stresses involved in remodeling, growth, and movement.

The involvement of extracellular matrix components, cell adhesion molecules, and cytoskeletal proteins in previously reported neural maintenance activities demonstrate that adhesive cell-matrix and possibly cell-cell interactions play a critical role (Aurelio et al. 2002; Bulow et al. 2004; Sasakura et al. 2005; Wang et al. 2005; Benard et al. 2006, 2009; Burket et al. 2006; Pocock et al. 2008; Woo et al. 2008; Zhou et al. 2008). Although previously unreported, factors controlling nuclear position in neurons may also be predicted to play key roles in positional maintenance of neuronal soma. Regulated movement of the cell nucleus is important in neuronal migration in the vertebrate cerebral cortex and retina (Nadarajah and Parnavelas 2002; Baye and Link 2008), and nucleus-cytoskeletal linkages have effects on cell rigidity and adhesion (Stewart-Hutchinson et al. 2008; Olins et al. 2009; Chancellor et al. 2010).

We report a genetic approach to identify and explore the role of two novel maintenance factors in stabilizing neuron cell body position in C. elegans. We find that the dystroglycan (DG) ortholog DGN-1 plays an important role in maintenance of cell body position in posterior lumbar ganglion neurons in C. elegans. In vertebrates, DG is a critical basement membrane receptor in skeletal muscle, in glia of both the central and peripheral nervous systems, and possibly in epithelia (Cohn et al. 2002; Michele et al. 2002; Moore et al. 2002; Muschler et al. 2002; Saito et al. 2003; Satz et al. 2009, 2010). Dystroglycan is expressed in neurons throughout the mouse brain (Zaccaria et al. …

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