TheC. elegansF-spondin family protein SPON-1 maintains cell adhesion in neural and non-neural tissues

Abstract

The F-spondin family of extracellular matrix proteins has been implicated in axon outgrowth, fasciculation and neuronal cell migration, as well as in the differentiation and proliferation of non-neuronal cells. In screens for mutants defective in C. elegans embryonic morphogenesis, we identified SPON-1, the only C. elegans member of the spondin family. SPON-1 is synthesized in body muscles and localizes to integrin-containing structures on body muscles and to other basement membranes. SPON-1 maintains strong attachments of muscles to epidermis; in the absence of SPON-1, muscles progressively detach from the epidermis, causing defective epidermal elongation. In animals with reduced integrin function, SPON-1 becomes dose dependent, suggesting that SPON-1 and integrins function in concert to promote the attachment of muscles to the basement membrane. Although spon-1 mutants display largely normal neurite outgrowth, spon-1 synergizes with outgrowth defective mutants, revealing a cryptic role for SPON-1 in axon extension. In motoneurons, SPON-1 acts in axon guidance and fasciculation, whereas in interneurons SPON-1 maintains process position. Our results show that a spondin maintains cell-matrix adhesion in multiple tissues.

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.…”

Role of the extracellular matrix in epithelial morphogenesis

“…In spon-1 mutants, the BM at the muscle-epidermis interface becomes convoluted, whereas in pxn-2 mutants it appears unstructured and very thick. 9,10 The significance of the muscleepidermis detachment and embryonic elongation defects in such mutants is further discussed in the third part of this review.…”

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration

“…RNA-mediated interference (RNAi) knockdown of spon-1 partially suppressed posterior AQR migration in mab-5(gof), suggesting that spon-1 mediates the effects of mab-5(gof) in posterior migration (Tamayo et al 2013). spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin (Woo et al 2008). In vertebrates, F-spondin is secreted by the floor plate of the neural tube and has multiple roles in neural adhesion, neural crest migration, and axon guidance (Klar et al 1992;Burstyn-Cohen et al 1999;Debby-Brafman et al 1999;Zisman et al 2007).…”

“…In addition to its role in disease, F-spondin is conserved in many species, including and has domain similarity to the established nervous system development molecule Reeler (Klar et al 1992;Higashijima et al 1997;Burstyn-Cohen et al 1999;Hu et al 2016). In C. elegans, SPON-1/F-spondin plays a role in neural adhesion and development (Woo et al 2008). spon-1 is required for muscle cell adhesion, and null or strong loss-of-function mutants are embryonic lethal (Woo et al 2008).…”