Researchers explore what makes us the size we are

by Nick Miller

That living beings come in all shapes and sizes is one of life’s great mysteries to scientist Jun Ma, PhD. It is also the focus of his life’s work.

The developmental biologist and his colleagues want to learn how — even in the environment of a frantic developmental process — embryos of different sizes manage to develop proportionally-sized body parts.

Ma’s team focuses largely on probing the role of a protein called Bicoid, and analyzing its target genes in early embryos. This allows the researchers to identify the genes and molecular pathways involved with Bicoid in normal embryonic development. The team studies the various genes’ expression levels, functionality and timing as they biochemically guide fruit fly embryos to form a normal developmental axis from head to tail.

Although fruit flies have miniscule brains and dine on rotten fruit, the insects are a valuable tool for studying clues about mammalian and human development. Through evolutionary conservation, many critical genes in fruit fly development are similar to genes in people.

Ma and his collaborators released two studies in the past year, published in Nature Communications and Development, that offer new insights on this developmental process. The Development study used female fruit flies selected to lay large or small eggs to show how the shape of the Bicoid protein gradient in the embryo adapts to its size. The Nature Communications study showed how Bicoid’s potency is regulated to control development.

“Traditionally, most studies investigate the importance of where a gene is expressed in controlling the outcome of a developmental process, as does our study in Development,” explains Ma, a member of the Divisions of Bioinformatics and Developmental Biology. “The Nature Communications paper reveals a new wrinkle It shows that the final developmental outcome is also sensitive to how much a gene product is expressed, as a result of how long the gene is kept on by the Bicoid protein.”

At their core, Ma says the studies help connect the concepts of time and space in explaining normal developmental patterns. The amount and distribution of the maternally-provided Bicoid protein give the embryo a first sense of its own size through activating a gene near mid-embryo. The length of time Bicoid activates this target gene determines how much gene product is made. Subsequently, this affects how body parts are further divided along the axis

If the process goes well, then developmental patterning and the proportional sizes of body parts should be normal. If not, nature could take some interesting twists and turns.

Many questions remain about how embryos of different sizes have the precise gene expression, timing and spacing they need to grow proportionally-sized parts. But in the process of one discovery leading to the next, Ma’s recent findings provide important clues.

“Although this would still need to be validated, if a normal developmental process depends on biochemical reactions that need to take place correctly in space and time,” he says, “this could help explain why different stages of a pregnancy may be sensitive to perturbations that can lead to defects.”