It has been said that nothing requires an architect’s care more than “due proportions.” What is true of buildings is also true of bodies, though the means by which bodies achieve their proportions are rather more mysterious than an architect’s whims. With bodies, much depends on genes, gene expression, and the localization and diffusion gradients of gene products called morphogens.
The idea of morphogens goes at least as far back as a paper published by Alan Turning in 1952 (“The Chemical Basis of Morphogenesis”). Since then, scientists have attempted to quantify the idea in various ways, often while relying on simple animal models, such as those provided by the Drosophila fruit fly.
The fruit fly is especially important because it helped scientists identify biocoid, the first known morphogen. And now bicoid figures in a new study, one that relates size and patterning accuracy of an embryo to the amount of reproductive resources mothers invest in the process before an egg leaves the ovary.
The new work, from scientists at Cincinnati Children’s Hospital Medical Center, appeared March 26 in Nature Communications, in an article entitled, “Fundamental origins and limits for scaling a maternal morphogen gradient.” The article describes a model called Tissue Expansion-Modulated Maternal Morphogen Scaling (TEM3S). It was used by the scientists to study scaled anterior–posterior patterning in Drosophila embryos.
“Using both ovaries and embryos, we measure a core quantity of the model, the scaling power of the bicoid (Bcd) morphogen gradient’s amplitude nA,” wrote the authors. “We also evaluate directly model-derived predictions about Bcd gradient and patterning properties.”
The scientists apparently had no difficulty sustaining their enthusiasm for this modeling effort, to judge by a statement made by Jun Ma, Ph.D., senior author and a scientist in the divisions of Biomedical Informatics and Developmental Biology. “One of the most intriguing questions in animal development is something called scaling, or the proportionality of different body parts,” she said. “Whether you have an elephant or a mouse, for some reason their organ and tissue sizes are generally proportional to the overall size of the body. We want to understand how you get this proportionality.”
The scientists learned that the size of fruit fly embryos depends on the quantity of initial tissue expansion in the mother's ovary—specifically the growth and size of the ovarian egg chamber and the expansion of bicoid gene copy numbers. This helps decide how large the mother fly’s 15 ovarian nurse cells will become, and how many duplicate copies of the fly’s genome and mRNA cells will contain. This trove of developmental resources all gets transferred to the oocyte that will become the future egg.
The TEM3S model lets researchers quantify the overall size of the mother fly's biological investment in this process. It also helps predict how that investment will determine the strength and robustness of the bicoid morphogen gradient that controls the proportion of body parts for her offspring. In short, a larger investment means a bigger return in the form of larger embryos that form well-proportioned body parts.
“Our results show that scaling of the Bcd gradient in the embryo originates from, and is constrained fundamentally by, a dynamic relationship between maternal tissue expansion and bcd gene copy number expansion in the ovary,” the authors concluded. “This delicate connection between the two transitioning stages of a life cycle, stemming from a finite value of nA~3, underscores a key feature of developmental systems depicted by TEM3S.”