Zygotic degradation of two maternal Cdc25 mRNAs terminates Drosophila's early cell cycle program.

Abstract

In Drosophila embryos the maternal/zygotic transition (MZT) in cell cycle control normally follows mitosis 13. Here we show that this transition requires degradation of two maternal mRNAs, string and twine, which encode Cdc25 phosphatases. Although twine is essential for meiosis and string is essential for most mitotic cycles, the two genes have mutually complementing, overlapping functions in the female germ line and the early embryo. Deletion of both gene products from the female germ line arrests germ-line development. Reducing the maternal dose of both products can lower the number of early embryonic mitoses to 12, whereas increasing maternal Cdc25 twi~e can increase the number of early mitoses to 14. Blocking the activation of zygotic transcription stabilizes maternal string and twine mRNAs and also allows an extra maternal mitosis, which is Cdc25 dependent. We propose that Drosophila's MZT comprises a chain reaction in which (1) proliferating nuclei deplete factors (probably mitotic cyclins) required for cell cycle progression; (2) this depletion causes the elongation of interphases and allows zygotic transcription; (3) new gene products accumulate that promote degradation of maternal mRNAs, including string and twine; and (4) consequent loss of Cdc25 phosphatase activity allows inhibitory phosphorylation of Cdc2 by Dweel kinase, effecting G2 arrest. Unlike timing or counting mechanisms, this mechanism can compensate for losses or additions of nuclei by altering the timing and number of the maternal cycles and thus will always generate the correct cell density at the MZT.

Cdc25 and the importance of G2control

“…Early Drosophila embryos express 2 homologs of Cdc25, String and Twine. 16 Recent studies in Drosophila have shown that onset of the MBT is due to rapid degradation of the Cdc25 ortholog Twine at the precise time the MBT begins, with the half-life of Twine changing from 20 min to 5 min (Fig. 2).…”

Zebrafish cdc25a is expressed during early development and limiting for post‐blastoderm cell cycle progression

“…In contrast, our observations are consistent with a gradual decay of maternally provided cdc25a message throughout gastrulation followed by dynamic spatially restricted expression upon completion of gastrulation. The drop in Cdc25 activity at the Drosophila MZT is required for a long G2 phase during cellularization of the embryo (Edgar and Datar, 1996), and is followed by pulses of string transcription that drive mitosis in domains corresponding to cell fate assignments. In zebrafish, only three mitotic domains have been described (Kane et al, 1992), and we see correlation between cdc25a expression and these domains.…”

“…Studies in Drosophila have established the importance of Cdc25 in coordinating cell proliferation with developmental events. Early synctial cell cycles are driven by maternally provided mRNA and protein from the Drosophila cdc25 homolog, string (Edgar and Datar, 1996). After the maternal-zygotic transition (MZT, cycle 10), maternal string mRNA is degraded (Edgar and Datar, 1996) and spatio-temporally patterned zygotic string expression begins (Edgar and O'Farrell, 1990).…”

“…Early synctial cell cycles are driven by maternally provided mRNA and protein from the Drosophila cdc25 homolog, string (Edgar and Datar, 1996). After the maternal-zygotic transition (MZT, cycle 10), maternal string mRNA is degraded (Edgar and Datar, 1996) and spatio-temporally patterned zygotic string expression begins (Edgar and O'Farrell, 1990). Expression of zygotic string mRNA anticipates mitoses in the early post-blastoderm cell cycles, and the highly stereotyped mitotic domains of the early Drosophila embryo correlate tightly with domains of string expression (Edgar and O'Farrell, 1990).…”

Steroid Hormones in Drosophila: How Ecdysone Coordinates Developmental Signalling with Cell Growth and Division

“…These include the Drosophila orthologue of the mammalian c-myc transcription factor and oncogene, dMyc, which drives growth and progression through G1 to S-phase (Johnston et al 1999), the essential G1 to S-phase Cyclin complex, Cyclin E (CycE) and its Cyclin-dependent-kinase (Cdk) partner Cdk2, which triggers S-phase by promoting DNA replication (Knoblich et al 1994;Neufeld et al 1998;Richardson et al 1995), and the Drosophila orthologue of the Cdc25 phosphatase, String (Stg), which is required for G2/M progression and promotes mitotic entry by activating the Cdk1/Cyclin B complex (Edgar and Datar 1996). CycE and Stg are the rate limiting factors for S-phase and mitosis, respectively, and both are activated by the Drosophila orthologue of human E2F1 protein, dE2F1 (Neufeld et al 1998).…”