Cytoskeletal machinery is used for both cell division and cell movement. For this reason,the cell cycle must be finely coordinated with motility. However, how this essential coordination is controlled remains unknown. During C. elegans gastrulation, two endodermal precursors, Ea and Ep, move into the center of the embryo and have a longer cell cycle than most of the cells at the same stage. Precocious Ea/p division in various mutant backgrounds is associated with gastrulation defects. However, a direct, causative relationship between cell cycle length and gastrulation has not been established. We asked if one of these genes,
gad-1 (Knight and Wood, 1998), was specifically required for gastrulation movements. By delaying Ea/p division with a laser, we were able to rescue ingression of Ea/p in
gad-1 mutant embryos, suggesting that
gad-1 indirectly causes gastrulation defects by affecting the timing of Ea/p division.We next asked whether or not a longer cell cycle was sufficient for ingression in other pairs of cells by laser-delaying their divisions. Surprisingly, we found that pairs of ABxx, MSxx, and Cxx cells were able to ingress given a longer cell cycle. This suggested that Ea/p ingress by virtue of their long cell cycle period, whereas other cells do not ingress due to shorter cell cycle periods. We are currently investigating the molecular mechanisms behind cell cycle control of ingression. One possible model is that a certain length of time in a specific phase of the cell cycle is required for gastrulation, and that laser treatment pauses the cells in that specific phase. Using pharmacological inhibitors of the cell cycle, as well as cell cycle mutants, we are attempting to identify if elongation of specific cell cycle phases is sufficient to rescue gastrulation in
gad-1 embryos. A second possible mechanism is that long cell cycle periods may allow an accumulation of proteins required for movement. We previously showed that ingression is driven by an actomyosin-based contraction of the apical side of Ea/p (Lee and Goldstein, 2003). Therefore, an attractive model is one whereby long cell cycle periods allow for the accumulation of molecules required for contractile forces at the apical surface of cells. One potential player we are currently examining with immunostaining is NMY-2, which was previously shown to localize and accumulate at the apical surface of Ea/p (Nance and Priess, 2002). Given the genetic, molecular, and embryological tools available for C. elegans, we hope to gain insight into the mechanisms through which the cell cycle controls cell movement.