Just as people in different places seem to operate at different rhythms, so too do different species. They age at their own rates: Some, like the fruit fly, race to adulthood so they can reproduce before their ephemeral food source disappears, while creatures like humans mature slowly over decades, in part because building a large, complex brain requires it. And at the very beginning of an embryo’s life, small tweaks in the timing of when and how different tissues develop can dramatically alter an organism’s form — a mechanism that evolution exploits in creating new species. However, what sets the tempo of an organism’s growth has remained a mystery.
“Our knowledge of what controls developmental timing has really lagged behind other areas in developmental biology,” said Margarete Diaz Cuadros, who leads research focused on developmental tempo at Massachusetts General Hospital in Boston.
Developmental biologists have had tremendous success in identifying networks of regulatory genes that talk to one another — cascading systems of feedback loops that turn genes on or off at exactly the right time and place to build, say, an eye or a leg. But the highly conserved similarity in these gene networks among species contrasts with huge differences in developmental timing. Mice and humans, for example, use the same sets of genes to create neurons and build spines. Yet the brain and spine of a mouse turn out quite differently than those of a human because the timing of when those genes are active is different, and it’s unclear why that’s so.
“Gene regulation does not seem to explain everything about developmental timing,” said Pierre Vanderhaeghen, who studies the evolution and development of the brain at KU Leuven in Belgium. “Now, this is a bit provocative because in a way, in biology, everything should be explained by gene regulation, directly or indirectly.”
New explanations for what makes life tick are emerging from innovations — like advances in stem cell culture and the availability of tools to manipulate metabolism, initially developed to study cancer — that now allow researchers to chart, and toy with, the pace of development of early embryos and tissues in greater detail. In a string of papers over the past few years, including one key publication in June, several research teams have independently converged on intriguing connections between the tempo of development, the pace of biochemical reactions, and rates of gene expression underlying those biochemical reactions.
Their findings point to a common metronome: the mitochondria, which may be the timekeeper of the cell, setting the rhythm for a variety of developmental and biochemical processes that create and maintain life. [Continue reading…]