spindle-C (spn-C) and okra (okr), cause a delay in oocyte determination and a failure to accumulate Grk protein, leading to defects in AP and DV patterning in late oogenesis

Polarization of the anteroposterior (AP) axis of the Drosophila oocyte occurs early in oogenesis, while the presumptive oocyte is still in the germarium (Gonzalez-Reyes and St Johnston, 1998). The dorsoventral (DV) axis is set up much later and relies on transfer of the AP axis polarity from the oocyte to the somatic follicle cells at the posterior end of the oocyte. During stages 4-6 in wild-type egg chambers, grk RNA that is localized next to the nucleus at the posterior end of the oocyte is translated and signals through the EGFR pathway to establish the adjacent follicle cells as posterior (GonzalezReyes et al., 1995). After these posterior follicle cells signal back to the oocyte, microtubule orientation in the oocyte is reversed, and the oocyte nucleus migrates along the microtubules to an anterior corner of the oocyte. During stages 8-9 this anterior corner is defined as dorsal by translation of grk RNA and activation of EGFR signaling in the overlying follicle cells (Gonzalez-Reyes et al., 1995; Neuman-Silberberg and Schupbach, 1994; Roth et al., 1995). Thus, grk signaling is required for elaboration of the AP axis and establishment of the DV axis. Recent results have shown that establishment of both AP and DV axes also depends on the successful repair of DNA double strand breaks (DSBs) that are formed during meiotic recombination (Ghabrial et al., 1998; Ghabrial and Schupbach, 1999). Meiotic prophase begins in early region 2a of the germarium, and both recombination and repair are probably completed before oocyte determination occurs in region 2b (Huynh and St Johnston, 2000). Meiosis and axis establishment are related to each other because the accumulation of Grk protein in the oocyte cytoplasm depends on the successful completion of meiotic recombination (Ghabrial et al., 1998; Ghabrial and Schupbach, 1999). Mutations in the spindle-class genes, spindle-B (spn-B), spindle-C (spn-C) and okra (okr), cause a delay in oocyte determination and a failure to accumulate Grk protein, leading to defects in AP and DV patterning in late oogenesis (Gonzalez-Reyes et al., 1997; Ghabrial and Schupbach, 1999). spn-B and okr encode Drosophila homologs of the RAD51 and RAD54 genes from yeast that are required for DSB repair (Ghabrial et al., 1998; Kooistra et al., 1997). Their effects on Grk appear to be mediated by a DNA damage checkpoint governed by Mei-41, a Drosophila member of the ATM/ATR family of kinases that are required for DNA damage and recombination checkpoints in yeast, worms and humans, as well as flies (reviewed by Melo and Toczysky, 2002; Weinert, 1998; Murakami and Nurse, 2000). Because they eliminate the checkpoint, mei-41 mutations suppress the effects of spn or okr mutations. The spn and okr mutations can also be suppressed by mutations in mei-W68, which encodes the Drosophila homolog of yeast gene SPO11, a gene required for the 5053 Development 129, 5053-5064 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV5517