PLK-1 asymmetry contributes to asynchronous cell division ofC. elegansembryos

Abstract

Acquisition of lineage-specific cell cycle duration is an important feature of metazoan development. In Caenorhabditis elegans, differences in cell cycle duration are already apparent in two-cell stage embryos, when the larger anterior blastomere AB divides before the smaller posterior blastomere P 1 . This time difference is under the control of anterior-posterior (A-P) polarity cues set by the PAR proteins. The mechanisms by which these cues regulate the cell cycle machinery differentially in AB and P 1 are incompletely understood. Previous work established that retardation of P 1 cell division is due in part to preferential activation of an ATL-1/CHK-1 dependent checkpoint in P 1 , but how the remaining time difference is controlled is not known. Here, we establish that differential timing relies also on a mechanism that promotes mitosis onset preferentially in AB. The polo-like kinase PLK-1, a positive regulator of mitotic entry, is distributed in an asymmetric manner in two-cell stage embryos, with more protein present in AB than in P 1 . We find that PLK-1 asymmetry is regulated by A-P polarity cues through preferential protein retention in the embryo anterior. Importantly, mild inactivation of plk-1 by RNAi delays entry into mitosis in P 1 , but not in AB, in a manner that is independent of ATL-1/CHK-1. Together, our findings support a model in which differential timing of mitotic entry in C. elegans embryos relies on two complementary mechanisms: ATL-1/CHK-1-dependent preferential retardation in P 1 and PLK-1-dependent preferential promotion in AB, which together couple polarity cues and cell cycle progression during early development.

The CRL2LRR-1 ubiquitin ligase regulates cell cycle progression during C. elegans development

“…LRR-1 has no impact, however, on the levels or localization of PLK-1 (data not shown) or CDC-25.1 (Fig. 5F), which localize asymmetrically between the AB and P1 blastomeres and regulate the AB-P1 asynchrony of cell division (Budirahardja and Gonczy, 2008;Rivers et al, 2008).…”

SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression

“…enrichment in AB of a positive regulator of mitotic entry, polo-like kinase 1 (PLK-1) (Budirahardja and Gonczy, 2008;Rivers et al, 2008).…”

Coordinating cell polarity with cell division in space and time

“…elegans one-cell embryos divide asymmetrically to form a larger anterior cell (AB) and a smaller posterior cell (P1). Cortical PAR polarity controls enrichment of the cytoplasmic mitotic kinase Polo-like kinase (PLK-1) at the anterior of the one-cell embryo [50][51][52]. As a result, AB inherits higher levels of PLK-1 at division.…”

“…As a result, AB inherits higher levels of PLK-1 at division. The higher PLK-1 levels drive AB into mitosis earlier than its posterior sister P1 [51,52]. par-3 mutants, which have low PLK-1 levels in both AB and P1, have a synchronous cell cycle at the two-cell stage, resembling the slower timing of the P1 cell.…”

“…par-3 mutants, which have low PLK-1 levels in both AB and P1, have a synchronous cell cycle at the two-cell stage, resembling the slower timing of the P1 cell. Conversely, par-2 mutants, which have high PLK-1 levels in both AB and P1, have a synchronous but fast cell cycle, as do AB cells [51,52]. In C. elegans embryos, therefore, polarity controls PLK-1 distribution, which in turn regulates asymmetric entry into the cell cycle of AB and P1.…”