Abstract
SummaryThe early cell divisions of many metazoan embryos are rapid and occur in the near absence of transcription. At the mid-blastula transition (MBT), the cell cycle elongates and several processes become established including the onset of bulk transcription and cell-cycle checkpoints. How these events are timed and coordinated is poorly understood. Here we show in Xenopus laevis that developmental activation of the checkpoint kinase Chk1 at the MBT results in the SCFβ-TRCP-dependent degradation of a limiting replication initiation factor Drf1. Inhibition of Drf1 is the primary mechanism by which Chk1 blocks cell-cycle progression in the early embryo and is an essential function of Chk1 at the blastula-to-gastrula stage of development. This study defines the downregulation of Drf1 as an important mechanism to coordinate the lengthening of the cell cycle and subsequent developmental processes.
Highlights
The early embryonic development of many animals, those that develop externally, involves a rapid expansion in cell numbers
We have shown in Xenopus laevis embryos that the increasing nuclear to cytoplasmic (N/C) ratio titrates out four replication initiation factors Drf1, Treslin, Recq4, and Cut5 (Collart et al, 2013)
In normal X. laevis embryos developing at 20C, the mid-blastula transition (MBT) occurs at 6.5–7.5 hr post (Bartek et al, 2004) or by inhibiting DNA replication
Summary
The early embryonic development of many animals, those that develop externally, involves a rapid expansion in cell numbers. These fast early cell divisions exhibit very little zygotic transcription and rely on maternally supplied products (Langley et al, 2014; Tadros and Lipshitz, 2009). After a species-specific number of rapid divisions, the cell cycle elongates and the zygotic transcriptional program is established. This developmental event is called the mid-blastula transition (MBT) or the maternal to zygotic transition (MZT; Tadros and Lipshitz, 2009). How the events of the MBT are timed and coordinated is poorly understood, yet these processes are critical for subsequent gastrulation when the three germ layers of the embryo are formed
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