Skip to main content
. 2018 Jul 18;145(14):dev156034. doi: 10.1242/dev.156034

Fig. 4.

Fig. 4. Mitotic-endocycle transitions in trophoblast giant cells. Cellular growth rates affect activation of E2F1-3, which control G1/S through transcriptional activation of S-CDK activity. E2F1-3 also activate expression of E2F7-8, which in turn repress expression of E2F1 and its targets, thus forming a negative-feedback loop. E2F1-3 are also required for the expression of cyclin A and cyclin B (CcnA and CcnB), which activate CDK1 (M-CDK) and are required for M-phase entry. M-CDK kinase activity activates the APC/C subunit Cdc20. The E3 ligase APC/CCdc20 targets geminin, CcnA and CcnB for proteasomal degradation. Depletion of geminin and M-CDK activity relieves inhibition of Cdt1 and creates a window of low CDK activity, respectively, which allows re-assembly of the pre-replication complex (pre-RC). In vitro, trophoblast stem cells are induced to enter endocycles upon FGF4 deprivation, which reduces CHK1 activity and relieves degradation of p57Kip2 and p21cip1. Accumulation of p57Kip2 and p21cip1 block M-CDK activity, which establish an M-phase bypass and onset of endocycles in TGCs. Further polyploidization is also affected by E2F7-8-dependent downregulation of E2F1-3.

Mitotic-endocycle transitions in trophoblast giant cells. Cellular growth rates affect activation of E2F1-3, which control G1/S through transcriptional activation of S-CDK activity. E2F1-3 also activate expression of E2F7-8, which in turn repress expression of E2F1 and its targets, thus forming a negative-feedback loop. E2F1-3 are also required for the expression of cyclin A and cyclin B (CcnA and CcnB), which activate CDK1 (M-CDK) and are required for M-phase entry. M-CDK kinase activity activates the APC/C subunit Cdc20. The E3 ligase APC/CCdc20 targets geminin, CcnA and CcnB for proteasomal degradation. Depletion of geminin and M-CDK activity relieves inhibition of Cdt1 and creates a window of low CDK activity, respectively, which allows re-assembly of the pre-replication complex (pre-RC). In vitro, trophoblast stem cells are induced to enter endocycles upon FGF4 deprivation, which reduces CHK1 activity and relieves degradation of p57Kip2 and p21cip1. Accumulation of p57Kip2 and p21cip1 block M-CDK activity, which establish an M-phase bypass and onset of endocycles in TGCs. Further polyploidization is also affected by E2F7-8-dependent downregulation of E2F1-3.