A role for the C. elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment

Abstract

The L1 family of cell adhesion molecules (L1CAMs) is important for neural development. Mutations in one of the human L1CAM genes, L1, can result in several neurological syndromes, the symptoms of which are variably penetrant. The physiological cause of these symptoms, collectively termed CRASH, is not clear. Caenorhabditis elegans animals genetically null for the L1CAM homologue LAD-1, exhibit variably penetrant pleiotropic phenotypes that are similar to the CRASH symptoms; thus the C. elegans lad-1 mutant provides an excellent model system to study how disruption of L1 leads to these abnormalities. These phenotypes include uncoordinated movements, variable embryonic lethality, and abnormal neuronal distribution and axon trajectories. Our analysis revealed that many of these phenotypes are likely a result of tissue detachment.

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

“…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 2006Burket 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.…”

“…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 2006Burket 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.…”

The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in Caenorhabditis elegans

“…Its precisely mapped and invariantly structured nervous system allows to probe with unprecedented detail the effect of removing individual cells and genes. Genetic and cellular ablation studies have revealed that a number of diverse Ig domain proteins are required to maintain the precise positioning of axons within fascicles and cell bodies within ganglia (Zallen et al 1999;Aurelio et al 2002;Bü low et al 2004;Sasakura et al 2005;Wang et al 2005;Bénard et al 2006;Pocock et al 2008). Intriguingly, without these molecules nervous system development is unaffected, yet precise neuroanatomical patterns are lost postdevelopmentally.…”

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

“…lad-2 encodes an L1CAM with conserved ectodomains but a divergent cytoplasmic tail that does not share any sequence homology with vertebrate L1CAMs (Wang et al 2008). In contrast, the sax-7 gene encodes a canonical L1CAM that more closely resembles vertebrate L1CAMs; both the ectodomains and intracellular motifs present in vertebrate L1CAMs are conserved in the SAX-7 protein (Chen et al 2001;Sasakura et al 2005;Wang et al 2005). sax-7 is required to maintain proper neuronal and axon positioning (Zallen et al 1999;Sasakura et al 2005;Wang et al 2005;Pocock et al 2008).…”

“…In contrast, the sax-7 gene encodes a canonical L1CAM that more closely resembles vertebrate L1CAMs; both the ectodomains and intracellular motifs present in vertebrate L1CAMs are conserved in the SAX-7 protein (Chen et al 2001;Sasakura et al 2005;Wang et al 2005). sax-7 is required to maintain proper neuronal and axon positioning (Zallen et al 1999;Sasakura et al 2005;Wang et al 2005;Pocock et al 2008). For example, GABAergic neurons are displaced in 95% of sax-7(eq1) adult animals (Wang et al 2005).…”