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

1184 Chapter 21: Development of Multicellular Organisms
Mutations affecting the regulation of Flc expression alter the time of flowering
and thus the ability of a plant to flourish in a given climate. The whole control system
governing the switch to flowering is thus of vital importance for agriculture,
especially in an era of rapid climate change.
The example of vernalization suggests a general point about the role of chromatin
modification in developmental timing. The plant uses changes in chromatin
to record its experience of prolonged cold. It may be that in other organisms—animals
as well as plants—slow, progressive changes in chromatin structure provide
long-term timers for those mysterious developmental processes that unfold
slowly, over a period of days, weeks, months, or years. Such chromatin timers may
be among the most important clocks in the embryo, but as yet we understand very
little about them.
Summary
Developmental timing is controlled at many levels. It takes time to switch a gene on
or off, and this time delay depends on the lifetimes of the molecules involved, which
can vary widely. Cascades of gene regulation involve cascades of delays. Feedback
loops can give rise to temporal oscillations in gene expression, and these may serve
to generate spatially periodic structures. During vertebrate segmentation, for example,
expression of the Hes genes oscillates, and one new pair of somites is formed
during each oscillation cycle. Hes genes encode transcription repressor proteins that
can act back on expression of the Hes genes themselves. This negative feedback generates
oscillations with a period that reflects the delay in the autoregulatory gene
switching loop. The period of oscillation of this “segmentation clock” controls the
sizes of the somites. Notch signaling between neighboring cells synchronizes their
oscillations: when Notch signaling fails, the cells drift out of synchrony because of
genetic noise in their individual clocks, and the segmental organization of the vertebral
column is disrupted.
Timing does not always depend on cell–cell interactions; many developing animal
cells have intrinsic developmental programs that play out even in isolated cells
in culture. Neuroblasts in Drosophila embryos, for example, go through set programs
of asymmetric divisions, generating different neural cell types at each division
with a predictable sequence and timing, through a cascade of gene switching
events. Studies in both vertebrates and invertebrates show that such programs are
rarely governed by the timing of cell division and can unfold even when cell division
is blocked. MicroRNAs produced at critical moments sharpen developmental transitions
by blocking the translation and promoting the degradation of specific sets
of mRNAs. Global coordination of developmental timing is achieved by hormones:
as a tadpole grows, for example, thyroid hormone levels surge and trigger its metamorphosis
into a frog. Environmental control of developmental timing is especially
striking in plants and reveals the presence of molecular timers that act over the long
term. In vernalization, for example, prolonged cold induces changes in chromatin
that chart the passage through winter so as to allow flowering only in the spring.
Slow, progressive changes in chromatin structure are likely to be important timers
in the long-term programming of development in animals too.
Morphogenesis
The specialization of cells into distinct types at specific times is important, but it
is only one aspect of animal development. Equally important are the movements
and deformations that cells go through to assemble into tissues and organs with
specific shapes and sizes. Like developmental timing, this process of morphogenesis
(“form generation”) is less well understood than the processes of differential
gene expression and inductive signaling that lead to cell-type specialization. The
cell movements can be readily described, but the underlying molecular mechanisms
that coordinate the movements are much harder to decipher.
In Chapter 19, we saw how cells cohere to form epithelial sheets or surround
themselves with extracellular matrix to create connective tissues. We also discussed
how the basic features of tissues, such as the polarity of epithelia, arise