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.