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
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the molecular lifetimes) for both the mRNA and the protein molecules. Somewhat
counterintuitively, it is the combined length of these delays, rather than the rate
of molecular synthesis (the number of molecules synthesized per second), that
chiefly determines the switching time.
The same additive principle applies to long cascades of gene switching, where
gene A activates gene B, and gene B activates gene C, and so on. It also applies
in other circumstances, such as in signaling pathways where one protein directly
regulates the activation of the next. In all these cases, molecular lifetimes, along
with gestation delays, play a key part in determining the pace of development.
The lifetimes of mRNA and protein molecules are enormously variable, from a few
minutes or hours to days or more, explaining much of the variation we see in the
tempo of developmental events.
Gene switching delays, however, are not the be-all and end-all of developmental
timing. Development involves many other kinds of delay that contribute
to timing. Chromatin structure takes time to remodel. Inductive signals take time
to diffuse across a field of cells (see Figure 21–9). Cells take time to move and rearrange
themselves in space. Nevertheless, the timing of gene switching plays a fundamental
part in developmental timing, as illustrated in an especially clear and
striking way by a gene-expression oscillator that controls the segmentation of the
vertebrate body axis, as we now explain.
A Gene-Expression Oscillator Acts as a Clock to Control
Vertebrate Segmentation
The main body axis of all vertebrates has a repetitive, periodic structure, seen in
the series of vertebrae, ribs, and segmental muscles of the neck, trunk, and tail.
These segmental structures originate from the mesoderm that lies as a long slab
on either side of the embryonic midline. This slab becomes broken up into a regular
repetitive series of separate blocks, or somites—cohesive groups of cells, separated
by clefts (Figure 21–38A). The somites form (as bilateral pairs) one after
another, in a regular rhythm, starting in the region of the head and ending in the
tail. Depending on the species, the final number of somites ranges from less than
40 (in a frog or a zebrafish) to more than 300 (in a snake).
The posterior, most immature part of the mesodermal slab, called the presomitic
mesoderm, supplies the required cells: as the cells proliferate, this mesoderm
(A)
(B)
cells arrested at trough
of oscillation cycle
oscillation
arrested
somite
neural tube
cells arrested at peak presomitic mesoderm
of oscillation cycle
most recently formed
pair of somites
oscillation
slowing down
oscillation
at 1 cycle every 90 min
1 mm
tail moves
back as new
somites form
Figure 21–38 Somite formation in the
chick embryo. (A) A chick embryo at 40
hours of incubation. (B) How the temporal
oscillation of gene expression in the
presomitic mesoderm becomes converted
into a spatial alternating pattern of gene
expression in the formed somites. In the
posterior part of the presomitic mesoderm,
each cell oscillates with a cycle time of 90
minutes. As cells mature and emerge from
the presomitic region, their oscillation is
gradually slowed down and finally brought
to a halt, leaving them in a state that
depends on the phase of the cycle they
happen to be in at the critical moment.
In this way, a temporal oscillation of gene
expression traces out an alternating spatial
pattern. (A, from Y.J. Jiang, L. Smithers and
J. Lewis, Curr. Biol. 8:R868–R871, 1998.
With permission from Elsevier.)