A role for septins in cellular and axonal migration in C. elegans

Abstract

Caenorhabditis elegans has two genes, unc-59 and unc-61, encoding septin-family GTPases. Mutations in the septin genes cause defects in locomotory behavior that have been previously attributed to cytokinesis failures in postembryonic neuroblasts. We find that mutations in either septin gene frequently cause uncoordination in newly hatched larvae in the absence of cytokinesis failures. The septins exhibit developmentally regulated expression, including expression in various neurons at times when processes are extending and synapses are forming. Motor neurons in the mutant larvae display defects in multiple aspects of axonal migration and guidance that are likely to be responsible for the locomotory behavior defects. The septins are also expressed in migrating distal tip cells, which are leaders for gonad arm extension. Septin mutants affect morphology of the distal tip cells, as well as their migration and guidance during gonadogenesis. These results suggest that septins may be generally required for developmental migrations and pathfinding.

The Flightless I Homolog, fli-1, Regulates Anterior/Posterior Polarity, Asymmetric Cell Division and Ovulation During Caenorhabditis elegans Development

“…The morphology of DTC was also abnormal in the fli-1 mutants. In wild-type young adult animals, the processes of DTC extend and branch down the side of the germline ( Figure 2E) (Finger et al 2003). In 72% of the fli-1 mutant young adults (n ¼ 45), the processes of the DTCs were much longer and disorganized ( Figure 2F).…”

“…Normally, in wild-type animals, the gonad migrates away from the mid-body region and then makes a turn from the ventral to the dorsal site. Finally, it reorients and migrates back toward the mid-body ( Figure 2G) (Finger et al 2003). However, in the fli-1 mutants, 67% of the gonad branches (n ¼ 102) migrated for only a short distance along the ventral bodywall muscles.…”

Some assembly required: yeast septins provide the instruction manual

“…Indeed, CDC3 and CDC12 are essential genes in S. cerevisiae and truncation of the CTEs that mediate their interaction is lethal, which indicates that formation of this minimal complex is required for septin function in vivo. Consistent with this view, the only septins in C. elegans are orthologs of Cdc3 and Cdc12 [40,41]. Only ARTS, an atypical septin-like protein in mitochondria [42], is suggested to function individually.…”

“…Both proteins (Unc-59 and Unc-61) colocalize at the midbody, and each requires the other for proper localization, and the phenotype of single mutants is identical to that of a double mutant [40,41]. Also, although there is no direct biochemical evidence for their physical association, Unc-59 and Unc-61 interact in two-hybrid studies [46].…”

Do septins have a role in cancer?

“…These latter data are complemented by Golgi reorientation assays that suggest that SEPT9_v4 can alter cell polarity. This is perhaps not surprising given the role of septins in determining polarity in yeast (Irazoqui and Lew, 2004) and Finger et al (2003) have shown that a nematode septin can profoundly influence directional movement of developing neurons. How SEPT9_v4 induces these phenotypes remains uncertain but it is of note that the normal association of other SEPT9 isoforms with filamentous structures is perturbed by SEPT9_v4 and the GV mutant thereof (Chacko et al, 2005).…”