UNC-52/Perlecan affects gonadal leader cell migrations in c. elegans hermaphrodites through alterations in growth factor signaling

Abstract

The unc-52 gene of Claenorhabditis elegans encodes a homologue of the basement membrane heparan sulfate proteoglycan perlecan. Viable alleles reduce the abundance of UNC-52 in late larval stages and increase the frequency of distal tip cell (DTC) migration defects caused by mutations disrupting the UNC-6/netrin guidance system. These unc-52 alleles do not cause circumferential DTC migration defects in an otherwise wild-type genetic background. The effects of unc-52 mutations on DTC migrations are distinct from effects on myofilament organization and can be partially suppressed by mutations in several genes encoding growth factor-like molecules, including EGL-17/FGF, UNC-129/TGF-beta, DBL-1/TGF-beta, and EGL-20/WNT. We propose that UNC-52 serves dual roles in C. elegans larval development in the maintenance of muscle structure and the regulation of growth factor-like signaling pathways.

Heparan 2-O-sulfotransferase,hst-2, is essential for normal cell migration inCaenorhabditis elegans

“…The migratory routing of the anterior DTCs is more frequently affected than the posterior DTCs in hst-2 mutants. Several mutants have been identified where the migration pathways of the anterior and posterior DTCs are differentially affected, suggesting that the migratory pathways of the DTCs are differentially regulated (39,40). The molecular nature of the growth factor and cell adhesion molecules affected in the hst-2 mutants warrants further work, but recent studies suggest several possible candidate genes.…”

“…The molecular nature of the growth factor and cell adhesion molecules affected in the hst-2 mutants warrants further work, but recent studies suggest several possible candidate genes. The C. elegans perlecan homologue, unc-52, which is expressed in the muscle (41), does not itself cause DTC migration defects but does in combination with the UNC-5͞netrin receptor and with growth factor mutations that cause aberrant DTC migrations (39). Unc-129͞TGF-␤ which is normally expressed in dorsal muscles, does not normally affect DTC migrations, but ectopic expression of unc-129 in ventral body wall muscles causes DTC migration defects (42).…”

“…Unc-129͞TGF-␤ which is normally expressed in dorsal muscles, does not normally affect DTC migrations, but ectopic expression of unc-129 in ventral body wall muscles causes DTC migration defects (42). Furthermore, unc-129 partially suppresses the enhancement by class I unc-52 alleles of unc-5(e152) DTC migration defects, suggesting genetic interactions of unc-52 with growth factors (39).…”

Syndecan regulates cell migration and axon guidance inC. elegans

“…Furthermore, sdn-1 null mutants exhibit no circumferential distal tip cell (DTC) migration defects. Mutations in the gene encoding perlecan/UNC-52, a basement membrane HSPG, enhance the DTC migration defects of UNC-6/netrin signaling mutants -an effect that can be partially suppressed by mutations disrupting growth factorlike signaling (Merz et al, 2003). Whether SDN-1 also contributes to signaling by EGL-20/WNT, UNC-129/TGF-␤ or EGL-17/FGF still needs to be determined.…”

Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina

“…To specifically test DTC function we down-regulated baf-1 in worms that express GFP under the control of the lag-2 promoter (strain jk2049), which marks DTCs (21). DTCs usually direct migration in three stages: first, away from the midbody, then, up (ventral to dorsal), and finally, back toward the midbody (22). Escapers were examined 1 week after hatching.…”