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.
Bibliographical noteFunding Information:
We thank S. Roth and B. Edgar for anti-Twist antibodies and for string cDNA, respectively, J. Grosshans for various fly stocks, the Bloomington Stock Center for various fly lines, the Developmental Studies Hybridoma Bank for anti-Neurotactin, and E. Schejter, Z. Paroush, B. Shilo, and S. Shwarzbaum for critical reading of the manuscript. This work was supported by grants from the Israeli Science Foundation (ISF) and the Israel Cancer Research Fund (ICRF).
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Agricultural and Biological Sciences (all)