Smith lab

Developmental Biology Laboratory

: The regulation of the cell cycle and of transcription at the mid-blastula transition

A developing mouse embryo.


Embryonic development is controlled initially by maternal transcripts and other factors that are laid down during oogenesis.

In Xenopus, bulk zygotic transcription begins after twelve rapid and synchronous cell cycles, at the so-called the midblastula transition (MBT). At this time cell cycles become asynchronous and longer; several proteins translocate from cytoplasm to nucleus; maternal mRNA is degraded; the apoptosis programme is engaged; cells become motile; karyomeres (individual chromosomes surrounded by a nuclear envelope) are replaced by conventional nuclei; the distance between origins of DNA replication increases; and DNA replication slows down.

In an effort to understand the MBT, we are asking whether these changes are all triggered by the same event, or whether one is primary and the others are initiated as a consequence. We focus on the changes in gene expression and in DNA replication that occur around the MBT.

High-resolution gene expression profiling of early Xenopus embryos reveals that there are distinct waves of gene expression: an early wave of polyadenylation of maternal transcripts followed by several waves of zygotic transcription. The experiments highlight the importance of maternal polyadenylation for the establishment of early zygotic transcription. Work in zebrafish embryos confirms that maternal transcripts provide the specificity required for proper initiation of zygotic transcription after genomic DNA acquires a competent state.

With respect to the cell cycle, we discovered that Y-RNAs become essential for DNA replication only after the MBT, and that four DNA replication factors-Cut5, RecQ4, Drf1 and Treslin-become limiting for the speed of DNA replication at the MBT. We are now exploring differences in the cell cycle before and after the MBT in more detail.

Selected publications