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First published online 8 October 2003
doi: 10.1242/dev.00790

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LET-99 opposes G/GPR signaling to generate asymmetry for spindle positioning in response to PAR and MES-1/SRC-1 signaling

Meng-Fu Bryan Tsou^*, Adam Hayashi and Lesilee S. Rose

Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA

Author for correspondence (e-mail: lsrose{at}ucdavis.edu)

Accepted 11 August 2003

G-protein signaling plays important roles in asymmetric cell division. In C. elegans embryos, homologs of receptor-independent G protein activators, GPR-1 and GPR-2 (GPR-1/2), function together with G (GOA-1 and GPA-16) to generate asymmetric spindle pole elongation during divisions in the P lineage. Although G is uniformly localized at the cell cortex, the cortical localization of GPR-1/2 is asymmetric in dividing P cells. In this report, we show that the asymmetry of GPR-1/2 localization depends on PAR-3 and its downstream intermediate LET-99. Furthermore, in addition to its involvement in spindle elongation, G is required for the intrinsically programmed nuclear rotation event that orients the spindle in the one-cell. LET-99 functions antagonistically to the G/GPR-1/2 signaling pathway, providing an explanation for how G-dependent force is regulated asymmetrically by PAR polarity cues during both nuclear rotation and anaphase spindle elongation. In addition, G and LET-99 are required for spindle orientation during the extrinsically polarized division of EMS cells. In this cell, both GPR-1/2 and LET-99 are asymmetrically localized in response to the MES-1/SRC-1 signaling pathway. Their localization patterns at the EMS/P₂ cell boundary are complementary, suggesting that LET-99 and G/GPR-1/2 signaling function in opposite ways during this cell division as well. These results provide insight into how polarity cues are transmitted into specific spindle positions in both extrinsic and intrinsic pathways of asymmetric cell division.

Key words: Asymmetric division, Polarity, Spindle orientation, C. elegans, Nuclear rotation

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