Abstract for CIE 2012 Special session on Morphogenesis
What about the horse part? Models of multicellular development.
James Sharpe
Coordinator of the EMBL-CRG Systems Biology Program
ICREA Research Professor
Centre for Genomic Regulation, Barcelona, Spain
During the embryonic development of a human hand hundreds of thousands of cells
multiply and change into different cell types to produce bone, cartilage, tendon, muscle,
nerve, blood and skin. A fundamental question concerns the spatial positioning of these
cells. Clearly, having the correct numbers of different cells is essential, but if they are not in
the correct positions the result is not a functioning hand. So, how do the different cells types
know where they should be in relation to each other?
Two distinct theoretical frameworks dominate the question of multicellular patterning:
Turing-type periodic patterning (Turing 1952), and positional information (Wolpert 1968).
They are correctly seen as fundamentally different: the latter emphasizes a de-coupling
between cellular position and cellular fate, while the former emphasizes a mechanism for
breaking spatial symmetry – diffusion-driven instabilities. The latter is invoked to explain the
specification of different structures in different positions (for example a head at one end,
and a tail at the other), while the former explains patterns such as zebra stripes, in which the
same cell fate (black pigment) occurs periodically at many different positions.
Over the last few decades, the popularity of the two ideas has tended to be mutuallyexclusive between two different research communities: positional-information being
popular amongst experimentalists, while Turing-type patterning being more popular
amongst theoreticians. This has led to a rather long period of divergence within the field.
During this time the relative importance of the two ideas has been hotly debated – almost as
if they were alternative explanations for the same phenomenon. Indeed, it was sometimes
highlighted that even Turing himself had originally questioned the importance of his idea,
apparently commenting on the zebra’s stripes by stating: “well the stripes are easy, but what
about the horse part?”
Recent years however, are seeing a convergence again, partly as it is increasingly recognized
that the two theories are not usually alternative explanations for the same phenomenon. In
this talk I will discuss the differences between the two ideas, the possible historical reasons
for the divergence, and the new emerging view which resolves the debate. Work in a
number of labs, including our own, is revealing that the patterning of many developmental
systems is in fact achieved by a close collaboration between both Turing-type mechanisms,
and positional information. In particular, our own work is highlighting the importance of
Turing-type mechanisms in two areas of skeletal patterning, showing that after all, Turing’s
idea does indeed contribute to “the horse part”.
A. Turing. (1952) The Chemical Basis of Morphogenesis. Philosophical Transactions of the
Royal Society of London. Series B, Biological Sciences, Vol. 237, No. 641. pp. 37-72.
L. Wolpert (1969) Positional information and the spatial pattern of cellular differentiation.
Journal of Theoretical Biology. Vol. 25, pp. 1-47.