Tissue growth is coupled to patterning during development
This relationship has been obvious since 1924 when Hans Speman and Hilde Mangold generated a second body axis by transplanting the blastopore lip of one newt embryo to another. This piece of organizing tissue (which, as we now know, produces powerful signalling molecules called morphogens) instructs the surrounding tissue, not only to differentiate new head structures, but also to grow by precisely the correct amount to accommodate them. In the almost 100 years that have followed, we have identified and studied these morphogens and others like them. We have a working understanding of the cellular machinery that transduces their signals and how they spread through tissue. We have outlined the basic principles by which morphogen gradients control gene expression to produce spatial patterns of tissue differentiation. But the coupling of patterning to growth is still a mystery. It’s not that we have not identified growth-promoting effectors that are activated by different types of morphogen signalling – at least in tumors. What we do not understand is how these two functions– growth and patterning – are logically linked together. How does morphogen signalling regulate the amount and orientation of tissue growth? What kind of feedback ensures that growth stops at precisely the size sufficient to produce the pattern of structures that must be built?
To control the amount and orientation of tissue growth, morphogen signalling must eventually act on the basic metabolic and mechanical properties of constituent cells. Our goal is to elucidate the connections between morphogen signalling, cell metabolism and cell mechanics and understand how their interactions combine to produce tissues of specific shapes and sizes.