Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

DEVELOPMENtaL TIMING
1181
time
first-stage
larva
second-stage
larva
third-stage
larva
fourth-stage
larva
wild
type
loss-of-function
Lin14 mutant
gain-of-function
Lin14 mutant
Increasing levels of Let7 miRNA govern the progression from late larva to adult.
In fact, Lin4 and Let7 were the first miRNAs to be described in any animal: it was
through developmental genetic studies in C. elegans that the importance of this
whole class of molecules for gene regulation in animals was discovered.
More generally, in many animals, miRNAs help regulate the transitions
between different stages of development. For example, in flies, fish, and frogs, the
maternal mRNAs that are loaded into the egg in the mother are removed during
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early development when the genome of the embryo begins to be transcribed; at
this stage, the embryo begins to express specific miRNAs that target many maternal
mRNAs for translational repression and degradation.
Thus, miRNAs can sharpen developmental transitions by blocking and removing
mRNAs that define an earlier developmental stage. But how is the timing of
miRNA expression itself controlled? In the case of the miRNAs that disable maternal
mRNAs in frogs and fish, expression is activated at the end of the series of
rapid, synchronous divisions that cleave the fertilized egg into many smaller cells.
As the division rate of these blastomeres slows, widespread transcription of the
embryo’s genome begins (Figure 21–43). This event, where the embryo’s own
genome largely takes over control of development from maternal macromolecules,
is called the maternal-zygotic transition (MZT), and it occurs with roughly
similar timing in most animal species, with the exception of mammals.
One trigger for the MZT appears to be the nuclear-to-cytoplasmic ratio.
During cleavage, the total amount of cytoplasm in the embryo remains constant,
but the number of cell nuclei increases exponentially. As a critical threshold is
reached in the ratio of cytoplasm to DNA, the cell cycles lengthen and transcription
is initiated. Thus, haploid embryos undergo the MZT one cell cycle later than
diploid embryos, which contain twice as much DNA per cell. According to one
Figure 21–42 Heterochronic mutations
in the Lin14 gene of C. elegans. Only the
effects on one of the many altered lineages
are shown. A loss-of-function (recessive)
mutation in Lin14 causes premature
occurrence of the pattern of cell division
and differentiation characteristic of a late
larva, so that the animal reaches its final
state prematurely and with an abnormally
small number of cells. The gain-of-function
(dominant) mutation has the opposite
effect, causing cells to reiterate patterns
of cell divisions characteristic of the first
larval stage, continuing through as many as
five or six molt cycles. The cross denotes
a programmed cell death. Green lines
represent cells that contain Lin14 protein
(which binds to DNA), red lines those that
do not. (Adapted from V. Ambros and
H.R. Horvitz, Science 226:409–416, 1984.
With permission from the authors; and
P. Arasu, B. Wightman and G. Ruvkun,
Genes Dev. 5:1825–1833, 1991. With
permission from the authors.)
mRNA levels
maternal-zygotic
transition
maternal
mRNAs
1 32 512
cell number
fertilization blastula
zygotic
mRNAs
gastrula
Figure 21–43 The maternal-zygotic
transition in a zebrafish embryo.
Maternal mRNAs are deposited by the
mother into the egg and drive early
development. These mRNAs are degraded
during different stages of embryogenesis,
including blastula and gastrula stages, but
a relatively abrupt change occurs at the
maternal-zygotic transition (MZT). Before
this, the embryonic (zygotic) genome is
transcriptionally inactive; afterward, zygotic
genes start to be transcribed. In zebrafish
embryos, the zygotic genome begins to be
activated at the 512-cell stage.
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