Caenorhabditis elegans dpy-24 integrates the temporal and spatial signals to control DTC migration
Date Issued
2009
Date
2009
Author(s)
Huang, Tsai-Fang
Abstract
Cell migration plays a key role in animal development and must be temporally and spatially regulated. However, little is known about how temporal and directional signals are integrated to give rise to specific cell migration patterns. In the C. elegans hermaphrodite, two somatic distal tip cells (DTC) undergo a developmental stage- and direction-specific migration pattern which determines the shape of the gonad. The heterochronic genes daf-12, dre-1 and lin-29, encoding steroid hormone receptor, F-box protein, and zinc finger transcription factor, respectively, act together to control the third larval (L3) developmental program of the gonad, including the ventral-to-dorsal migration of the DTCs. The guidance receptor unc-5 is both necessary and sufficient for dorsal migration of the DTCs away from the ventrally concentrated extracellular cue netrin. Here, we identify and characterize dpy-24 mutants and show that dpy-24 links the L3 temporal signal to the spatial regulator unc-5 and thereby controls the timing of DTC dorsal migration. Mutations in dpy-24 results in precocious dorsalward turning of the DTCs, whereas constitutive expression of dpy-24 leads to retarded DTC dorsal turn. dpy-24 encodes a zinc-finger-containing protein, similar to mammalian transcription repressors Blimp-1 and PRDI-BF1. Using an unc-5 transcriptional gfp reporter, we show that dpy-24 prevents the DTCs from precocious dorsal turn by transcriptional repression of unc-5. The immunostaining data reveals that DPY-24 is present in the DTCs prior to their dorsalward turning and disappears during and after the dorsal turn. Further studies indicate that dre-1, daf-12 and lin-29 are responsible for DPY-24 down-regulation at the L3 stage. DPY-24 protein level is high in L2 and thus prevents DTC from dorsalward turning. The timely disappearance of DPY-24, which is regulated by L3-specific temporal signal, leads to concomitant unc-5 transcriptional up-regulation, likely mediated through transcription activities of LIN-29 and DAF-12, hence allowing DTC migration to switch towards the dorsal direction. These results provide a molecular mechanism by which temporal and spatial signals are integrated to control the precise cell migration pattern during development.
Subjects
cell migration
temporal regulation
distal tip cell (DTC)
heterochronic
unc-5
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