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

1176 Chapter 21: Development of Multicellular Organisms
Sog. This creates a gradient of Dpp activity that helps refine the assignment of different
characters to cells at different positions along the D-V axis.
In Xenopus, the polarity of the egg and the site of sperm entry set up the embryonic
axes. A gradient generated by the TGFβ-family protein Nodal induces different
fates along the animal-vegetal axis, whereas BMP and Chordin—proteins homologous
to Drosophila Dpp and Sog, respectively—control the patterning of the D-V
axis. This axis is inverted, so that dorsal in the fly corresponds to ventral in the frog.
Transcription regulators control the formation of specific cell types. Members
of the MyoD/myogenin family drive the process of muscle cell determination, coordinating
the many components required, whereas Achaete/Scute transcription
regulators control neural fate. Other genes encoding such master transcriptional
regulators can regulate the formation of entire organs. Eyeless, for example, is both
necessary and sufficient to generate eye structures in Drosophila.
To refine the anatomical pattern within such an organ, the cells interact locally,
both by diffusible inductive signals and by short-range mechanisms. Often, the cells
compete with one another by lateral inhibition. This process results in activation of
the Notch signaling pathway in one cell and inhibition in its neighbors, generating
two different cell types. Asymmetric cell divisions, in which daughter cells inherit
different molecular determinants from the mother cell, provide an additional way
to organize a fine-grained diversity of cell types.
Evidence from recent evolutionary events indicates that anatomical changes are
mostly driven by changes in regulatory DNA sequences that determine when and
where developmental genes are expressed. How the striking diversity in body structures
has evolved over longer times remains largely unknown, although it seems
likely that similar principles apply.
Developmental Timing
Developmental events unfold over minutes, hours, days, weeks, months, or even
years, with each organism following its own strict timetable. The cascades of
inductive interactions and transcriptional regulatory events described earlier take
time, as signals are transmitted and transcription regulators are synthesized and
then bind to DNA to activate or repress their target genes. At the beginning of this
chapter, we compared development with an orchestral performance. There are
many players, and each must do the right thing at the right time; yet there is no
leader or conductor to set the tempo and coordinate the timing of all the different
events. Each developmental process must thus occur at an appropriate rate,
tuned by evolution to fit with the timing of other processes in the embryo or in
the environment. The control of timing is one of the most important problems in
developmental biology, but also one of the least understood.
Molecular Lifetimes Play a Critical Part in Developmental Timing
Developmental processes are complex, but they are built up from simple steps. A
first challenge is to understand the timing of these steps. How long does it take,
for example, to switch the expression of a gene on or off? This is not like throwing
a light switch: it involves delays. First, it takes time to make an mRNA molecule:
the RNA polymerase must travel the length of the gene, the primary RNA transcript
must be spliced and otherwise processed, and the resulting mRNA must
be exported from the nucleus and delivered to the site where it will be translated.
This adds up to what one might call the gestation time of the individual molecule.
Second, it takes time for the individual mRNA molecules to accumulate to their
fully effective concentration; as explained in Chapter 15, this accumulation time is
dictated by the average lifetime of the molecules—the longer they last, the higher
their ultimate concentration, and the longer the time taken to attain it. Similar
delays occur at the next step, where the mRNA is translated into protein: synthesis
of each individual protein molecule involves a gestation delay, and attainment of
an effective concentration of protein molecules involves an accumulation delay
that depends on the protein’s lifetime. The time for the whole gene switching process
is just the sum of the gestation delays and the accumulation delays (basically,