442
activation begins. These events, along with clearance of maternal RNAs and proteins,
define the maternal to zygotic transition and are coordinated at a developmental mile-
stone termed the midblastula transition (MBT). Despite the relative quiescence of the
zygotic genome in vertebrate embryos, genes required for clearance of maternal
RNAs and for the initial steps in mesoderm induction are robustly transcribed before
MBT. The coordination and timing of the MBT depends on a mechanism that senses
the ratio of nuclear to cytoplasmic content as well as mechanisms that are independent
of the nuclear–cytoplasm ratio. Changes in chromatin architecture anticipate zygotic
gene activation, and maternal transcription factors identified as regulators of pluri-
potency play critical roles in kick-starting the transition from the proliferative, plu-
ripotent state of the early embryo to the more lineage-committed phase of development
after the MBT. This chapter describes the regulation of the cell cycle and the activa-
tion of zygotic gene expression before and after the MBT in vertebrate embryos.
Keywords Midblastula transition • Maternal zygotic transition • Zygotic transcrip-
tion • Cell cycle checkpoint • Embryo • DNA damage • Nuclear cytoplasmic ratio
- Cell cycle • Pluripotency
9.1 Introduction
Many metazoan embryos initiate development with a series of rapid, synchronous
divisions that lack G1 and G2 phases, leading to reduction in cell size with each
subsequent division (Bachvarova et al. 1966 ; Graham and Morgan 1966 ; Newport
and Kirschner 1982a; Tadros and Lipshitz 2009 ; Gerhart 1980 ; Davidson 1986 ;
Baroux et al. 2008 ). Rapid cleavage divisions are typically observed in embryos of
vertebrates with larger eggs, such as amphibians, fish, birds, and reptiles. Although
mammalian embryos undergo slower, asynchronous cell cycles from the outset,
both mammalian and nonmammalian vertebrate embryos delay the onset of zygotic
transcription and depend initially on maternal mRNAs and proteins to direct the
earliest stages of development.
Rapid cell divisions and global suppression of zygotic transcription during cleav-
age stages require unique adaptations for the control of DNA replication, mitosis,
and early gene expression. During the transition from maternal to zygotic control of
development, maternal mRNAs are degraded, the cell cycle lengthens, cell divisions
become asynchronous, cells become motile, and large-scale zygotic transcription
begins. In amphibians and fish, as well as invertebrates such as Drosophila, the
appearance of gap phases (G1 and G2) in the cell cycle and the onset of large-scale
zygotic transcription occur predictably after a species-specific number of cell/nuclear
divisions, termed the midblastula transition (MBT). While not all organisms coordi-
nate the cell cycle changes with the onset of zygotic transcription (mammalian cell
cycles are initially slow, whereas sea urchins undergo rapid cleavages but initiate
zygotic transcription at fertilization), there are nevertheless conserved features in the
regulation of cell cycle and transcription that are reviewed in this chapter.
M. Zhang et al.