MRC National Institute for Medical Research, London
Science for Health
Morphogen gradients not needed for proliferation
07 October 2009
How organ size is determined during development has become an important question. Morphogens (secreted molecules that control cell fate decisions) have been implicated in organ size determination. Indeed, in wing imaginal discs of Drosophila, a block in morphogen signalling leads to premature proliferation arrest. For example, in the absence of Wingless, an important morphogen, wings remain stunted. Importantly, the proliferation rate is uniform in prospective wing tissue even though morphogen distribution is graded. One model to explain how graded morphogen signalling leads to uniform proliferation is that the spatial derivative of morphogen level could be the key regulatory feature.
Alberto Baena-Lopez, Xavi Franch-Marro and Jean-Paul Vincent (pictured), in NIMR's Division of Developmental Neurobiology, have devised a test of this model by removing all endogenous Wingless and replacing it with uniform and moderate exogenous signalling. This led to a complete rescue of proliferation and restored normal wing size, a clear demonstration that Wingless signalling stimulates growth in a gradient independent manner. In addition, they have shown that only low or moderate signalling promotes proliferation. As shown by others before, high signalling leads to proliferation arrest. The NIMR team has shown that since the normal Wingless gradient is very steep, a relatively small number of cells are exposed to high level Wingless (and do not proliferate) while most cells receive a low level that is appropriate for proliferation.
Wingless signaling promotes cell proliferation in a gradient-independent manner
On the left: Imaginal discs and wings comprising a posterior compartment composed entirely of wingless mutant cells.
On the right: Same genotype as on the left except that, in addition, all the cells of the posterior compartment express uniform and moderate Wingless from a transgene. Note the rescued wing size in F.
Thanks to technical developments in our lab and to the keen observational power of Alberto and Xavi, we were able to devise a stringent test of the effect of graded signalling on growth. Of course, Wingless is just one of the signals that controls proliferation so the challenge now is to understand how the effects of all the factors that impinge on proliferation and apoptosis are integrated so that appendages always end up with the correct size and shape.
Jean-Paul Vincent
Original article
Luis Alberto Baena-Lopez, Xavier Franch-Marro and Jean-Paul Vincent (2009) Wingless promotes proliferative growth in a gradient-independent manner Science Signaling , 180:674-683. Publisher abstractSee also
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