How much do the experiences we accumulate in childhood shape our brain development? A new study from the Hobert Lab published in Science Advances addresses this question in the small roundworm (and champion of biology research) C. elegans, and reports the discovery of a mechanism by which early-life experiences shape nervous system development.
This study was led by Dr. Chien-Po Liao, a postdoctoral researcher in the lab who studies how periods of starvation early in C. elegans development can change the physical wiring of the roundworm’s neural circuitry. Liao discovered that when young worms endure periods of starvation, their serotonin signaling is disrupted, and this lack of proper serotonin signaling leads to differences in gene expression that ultimately lead to lasting changes in the worms’ neural circuits. Fascinatingly, this change only happens in male worms, revealing a way in which developing brains respond differently to experience in a sex-dependent way.
Liao’s research also revealed that the master gene regulating brain development in response to early-life starvation is called lin-29a, whose expression requires serotonin signaling from feeding. When the serotonin signaling is lost, lin-29a is unable to be expressed at the right time in development, leading to deficits in the number and size of synapses between specific neurons in the worm. The nature of the affected cells and the precise gene regulation events leading to such changes have been worked out in great detail by Liao and the Hobert lab.
“The most exciting aspect of this study,” says Liao, “is its discovery of a transcriptional cascade linking early-life experiences to sex-specific brain wiring, showcasing a mechanism that integrates four layers of information – sexual specificity, past experience, time, and cell-type specificity.” Finding causal mechanisms for how physical brain development is impacted by its environment is no easy task, and finding a mechanism that integrates just one of these layers of information would be enough of a finding for its own publication.
This discovery adds to the field’s understanding of the complex interplay between our hard-wired genetic code and a constantly changing environment, offering concrete molecular evidence for how brain development in certain sexes might be more vulnerable to environmental risks. In the great debate of whether nature or nurture dictates our development, it seems as though the true winner is both—and in a much more complex way than we could have imagined.
