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

MECHANISMS OF patterN FORMatION
1155
cell’s internal state. Thus, a succession of simple cues that a cell receives at different
times can direct it along a complex developmental pathway. At each step, the cell
becomes further restricted in the range of final states open to it. The process reaches
its limit when the cell differentiates to form one of the specialized cell types of the
adult body.
Differences between developing cells arise in various ways and have to be properly
coordinated in space. In one common strategy, initially similar cells within
a group become different by exposure to different levels of an inductive signal or
morphogen emanating from a source outside the group. Neighboring cells can also
become different by lateral inhibition, in which a cell signals to its neighbors not to
follow the same fate. These cell–cell interactions are mediated by a small number of
highly conserved signaling pathways, which are used repeatedly in different organisms
and at different times during development. Not all cell diversification arises
by cell–cell interactions, however: daughter cells can be born different as a result of
asymmetric cell division.
Regulators of transcription and chromatin structure bind to regulatory DNA
and determine the fate of each cell. Differences of body plan seem to arise to a large
extent from differences in the regulatory DNA associated with each gene. This DNA
has a central role in defining the sequential program of development, calling genes
into action at specific times and places according to the pattern of gene expression
that was present in each cell at the previous developmental stage.
Development has been most thoroughly studied in a handful of model organisms.
But most of the genes and mechanisms thereby identified are used in all animals
and repeatedly at different stages of development. Thus, insights from worms,
flies, fish, frogs, and mice deeply inform our understanding of embryology, birth
defects, and adult tissue maintenance in humans.
Mechanisms of Pattern Formation
A developing multicellular organism has to create a pattern in fields of cells where
there was little or none before. Some of the early microscopists imagined the
entire shape and structure of the human body to be already present in the sperm
as a “homunculus,” a miniature human; after fertilization, the homunculus would
simply grow and generate a full-sized human. We now know that this view is
incorrect and that development is a progression from simple to complex, through
a gradual refinement of an animal’s anatomy. To see how the whole sequence of
events of spatial patterning and cell determination is set in train, we must return
to the egg and the early embryo.
Different Animals Use Different Mechanisms to Establish Their
Primary Axes of Polarization
Surprisingly, the earliest steps of animal development are among the most variable,
even within a phylum. A frog, a chicken, and a mammal, for example, even
though they develop in similar ways later, make eggs that differ radically in size
and structure, and they begin their development with different sequences of cell
divisions and cell specializations. Gastrulation occurs in all animal embryos, but
the details of its timing, of the associated pattern of cell movements, and of the
shape and size of the embryo as gastrulation proceeds are highly variable. Likewise,
there is great variation in the time and manner in which the primary axes of
the body become marked out. However, this polarization of the embryo usually
becomes discernible very early, before gastrulation begins: it is the first step of
spatial patterning.
Three axes generally have to be established. The animal-vegetal (A-V) axis,
in most species, defines which parts are to become internal (through the movements
of gastrulation) and which are to remain external. (The bizarre name dates
from a century ago and has nothing to do with vegetables.) The anteroposterior
(A-P) axis specifies the locations of future head and tail. The dorsoventral (D-V)
axis specifies the future back and belly.