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studied using simple assays for gene expression such as Northern blots, PCR bands or micro-
arrays, and the control of gene expression can be investigated by mutating a one-dimensional
length of DNA and monitoring the effects; much of this work can even be done in cell-free
systems. Communication can be studied by grafting pieces of embryo to identify the pres-
ence of signalling events, and then testing the ability of candidate signalling molecules to
drive developmental events by removing the candidates or applying them ectopically.
Even these experiments, which use limited numbers of components and usually simple assay
systems, can be difficult and time-consuming. However, when performed well, they usually
generate clear and unambiguous results. For this reason, study of differentiation and
communication has dominated developmental biology in the molecular era.
The result of this has been a vastly improved knowledge of how plants and animals develop
as well as a new understanding of the molecular bases of human congenital disease. The best
textbooks of the pre-molecular era were dominated by descriptive embryology and by specu-
lation about mechanisms, this speculation being basedmainly on extrapolation fromunusually
tractable but dangerously distant models (such as gene control in viruses). These topics, which
provided the foundations onwhich programs of molecular biology could stand, have been suc-
ceeded in recent years by large and solid works full of well-established mechanisms of signal-
ling, pattern formation and gene control. 5,6,7,8 Readers under the age of about 45 will no doubt
have been guided into developmental biology by one of these excellent volumes.
What has been gained has been a triumph, but it has created a temporary imbalance in the
field of developmental biology. The spotlight of developmental topic and review volumes is
usually focused on the molecular biology of gene control and pattern formation. Morphogen-
esis, the deep developmental question that held centre stage of embryological thought for
over two millennia, has been somewhat eclipsed. This shows up in several ways. Most obvi-
ously, it shows up in the proportion of pages that current texts devote to molecular mech-
anisms of morphogenesis, compared with those devoted to other aspects of developmental
biology; in the currently popular and excellent general textbooks of developmental biology,
this proportion is generally less than 10 percent and is sometimes close to zero. The taking for
granted of morphogenetic mechanisms also shows up, more subtly, in the 'blob and arrow'
diagrams often used to summarize developmental pathways. These tend to show numerous
arrows between genes and promoters and signalling pathways that set up the control logic
for a developmental event. These arrows then point to 'black boxes' in which the actual mor-
phogenesis d the point of all that lies above them in the diagram d actually takes place
( Figure 1.1 ). The reason for the black boxes is obvious; for the most part morphogenesis still
is a 'black box', the inner workings of which remain mysterious. And, lest I have offended
anyone by the comments in this paragraph, I stress that many of my own reviews on organ
development 9,10,11,12,13,14 have been as full of black boxes that stand for morphogenesis as
anyone else's have been, for the same reason.
The approach to 'insoluble' problems that was recommended by Medawar is, however,
starting to pay off. When molecular biological techniques were first applied to embryonic
development, it would have been impossible to solve the problems of morphogenesis
directly. Even where the reasonableness of hypothetical mechanisms could be confirmed
by computer modelling (see Chapter 26), it was generally not possible to verify them in
real developing systems. The great advances in our understanding of the molecular genetics
of development and of
the biochemistry of cell signalling may have unbalanced
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