Cell divisions in the drosophila embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by HOW.
BACKGROUND: Cell-cycle progression is tightly regulated during embryonic development. In the Drosophila early embryo, the levels of String/Cdc25 define the precise timing and sites of cell divisions. However, cell-cycle progression is arrested in the mesoderm of gastrulating embryos despite a positive transcriptional string/cdc25 activation provided by the mesoderm-specific action of Twist. Whereas String/Cdc25 is negatively regulated by Tribbles in the mesoderm at these embryonic stages, the factor(s) controlling string/cdc25 mRNA levels has yet to be elucidated. RESULTS: Here, we show that the repressor isoform of the Drosophila RNA binding protein Held Out Wing [HOW(L)] is required to inhibit mesodermal cell division during gastrulation. Embryos mutant for how exhibited an excess of cell divisions, leading to delayed mesoderm invagination. The levels of the mitotic activator string/cdc25 mRNA in these embryos were significantly elevated. Protein-RNA precipitation experiments show that HOW(L) binds string/cdc25 mRNA. Overexpression of HOW(L) in Schneider cells reduces specifically the steady-state mRNA levels of a gfp reporter fused to string/cdc25 untranslated region (3'UTR). CONCLUSIONS: Our results suggest that in wild-type embryos, string/cdc25 mRNA levels are downregulated by the repressor isoform HOW(L), which binds directly to string/cdc25 mRNA and regulates its degradation. Thus, we are proposing a novel posttranscriptional mechanism controlling cell-cycle progression in the Drosophila embryo.[1]References
- Cell divisions in the drosophila embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by HOW. Nabel-Rosen, H., Toledano-Katchalski, H., Volohonsky, G., Volk, T. Curr. Biol. (2005) [Pubmed]
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