Syndecan regulates cell migration and axon guidance inC. elegans

Abstract

During nervous system development, axons that grow out simultaneously in the same extracellular environment are often sorted to different target destinations. As there is only a restricted set of guidance cues known,regulatory mechanisms are likely to play a crucial role in controlling cell migration and axonal pathfinding. Heparan sulfate proteoglycans (HSPGs) carry long chains of differentially modified sugar residues that have been proposed to encode specific information for nervous system development. Here, we show that the cell surface proteoglycan syndecan SDN-1 functions autonomously in neurons to control the neural migration and guidance choices of outgrowing axons. Epistasis analysis suggests that heparan sulfate (HS) attached to SDN-1 can regulate guidance signaling by the Slit/Robo pathway. Furthermore, SDN-1 acts in parallel with other HSPG core proteins whose HS side chains are modified by the C5-epimerase HSE-5, and/or the 2O-sulfotransferase HST-2, depending on the cellular context. Taken together, our experiments show that distinct HS modification patterns on SDN-1 are involved in regulating axon guidance and cell migration in C. elegans.

The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons inC. elegans

“…In C. elegans, PVPR pioneer axon navigation defects observed in fmi-1-deficient animals are also reported for several other genes, e.g. the basement membrane components UNC-6/NETRIN and NID-1/NIDOGEN, the IgCAMs WRK-1 and SAX-3/ROBO, the Fatlike cadherin CDH-4, and the SYNDECAN ortholog SDN-1 (Boulin et al, 2006;Hutter, 2003;Rhiner et al, 2005;Schmitz et al, 2008;Schwarz et al, 2009). fmi-1-deficient animals, as well as lin-17/frizzled, cdh-4 and nid-1 mutants, show highly penetrant PVPR defects, suggesting that in this complex network of guidance cues, these molecules might play a central role for correct axon navigation and midline avoidance of the PVPR pioneer axon.…”

The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance

“…For example, in both Drosophila and C. elegans, syndecan regulates slit-Robo-mediated midline guidance events (Hu 2001;Johnson et al 2004;Steigemann et al 2004;Rhiner et al 2005), and in Drosophila, dally-like can compensate for the loss of syndecan (Johnson et al 2004). In contrast, during visual system assembly and synaptic development, there is only limited rescue of syndecan mutant defects with dallylike transgenes and vice versa; this suggests that dallylike and syndecan can serve distinct functions .…”

PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation

“…The native HSPGs involved in this process are not known and require further investigation, however, several HSPGs are expressed in Xenopus embryos in tissue specific patterns during gastrulation including Syndecans-1 and -2 [expressed in the ectoderm (44)] and Syndecan-4, Glypican-4, and Biglycan [expressed in the ectoderm and mesoderm (44)(45)(46)(47)]. Although the role(s) of these HSPGs in mesendoderm migration have not been investigated, they are involved in a wide range of processes that involve cell rearrangements including embryonic development, wound healing, angiogenesis, neuronal cell migration and cancer cell invasion through their interactions with ECM molecules, growth factors, cytokines, and chemokines (38,(48)(49)(50)(51). For example, as discussed above, knock-down of either Syndecan-1 or -2 disrupts the blastocoel roof ECM and results in gaps in fibril deposition (38).…”