線蟲性腺發育過程中MOM-5/Frizzled 在前後端遠頂細胞啟動相反的訊息去引導其遷移

Abstract

Cell migration plays an important role during animal development. The gonadogenesis of the C. elegans hermaphrodite is guided by stage-specific migration of two leader cells, distal tip cells (DTCs). These cells undergo three sequential phases of migration-centrifugal, dorsal and centripetal-during larva stages and lead the formation of U-shaped gonad arm. Although the guidance cue netrin has been shown to control the dorsal migration of the DTCs, the guidance systems that regulate their longitudinal migration is still unclear. In addition, the temporal control of these spatial migrations is poorly understood. We find that MOM-5, a Frizzled receptor (Fz), is required for the proper DTC centripetal migration specifically at the 4th larval stage and that all five wnts are involved in this process. Four of the wnts signal to MOM-5 in promoting correct pathfinding, while the other one seems to act in suppression of MOM-5. Using the gfp reporter, we find that mom-5 is transcriptionally upregulated in the DTCs at the 4th larval stage, consistent with its cell-autonomous function in DTC centripetal migration. Overexpression of MOM-5/Fz using various promotors results in the L4-specific pathfinding defect, indicating that the regulation of the MOM-5/Fz level is critical for the correct centripetal migration at L4. Moreover, our genetic analysis suggests that MOM-5/Fz may acts upstream of DSH-1/Dsh and CED-5/GEF, but in paralle to CED-2/CrkII, in the signaling pathway to regulate the L4-specific DTC centripetal migration, at least in the anterior DTC migration Together, our work shows that MOM-5/Fz acts with specific wnts to guide the centripetal migration of DTCs at the 4th larval stage and may define a novel signaling pathway involving CED-5/GEF but not CED-2/CrkII