Debunking a Decades-Long Misconception about the Origin of the Vertebrate Sympathetic Nervous System

For decades, researchers believed that lamprey—eel-like jawless fish—did not have sympathetic neurons, which are a part of the peripheral nervous system. The sympathetic nervous system is made up of nerves that target internal organs throughout the body, including the heart, pancreas, and gut. Persistent activity of the sympathetic nervous system is required to maintain homeostasis, as it modulates processes such as cardiac output, blood glucose monitoring, and digestion. The system is also best known for mediating the fight-or-flight response in vertebrates.

Lamprey, or Petromyzon marinus, are the closest thing we have today to studying the ancient fish ancestors from which we evolved 550 million years ago. Researchers in the laboratory of Marianne Bronner, Edward B. Lewis Professor of Biology and director of the Beckman Institute, use lamprey to study how developmental changes may have promoted progressive evolution of vertebrate traits. Now, new research from Bronner's lab finds sympathetic neurons in lamprey, revising the timeline of sympathetic nervous system evolution.

"Over a hundred years of literature has suggested that lamprey lack a sympathetic nervous system," says Bronner. "Surprisingly, we found that sympathetic neurons do, in fact, exist in lamprey but arise at a much later time in lamprey development than expected."

The research was led by postdoctoral scholar Brittany Edens and is described in a paper appearing on April 17 in the journal Nature.

Bronner's laboratory studies neural crest cells, a kind of stem cell specific to vertebrates that gives rise to various cell types throughout the body. Until this study, it was thought that lamprey lacked the neural crest-derived precursors, or progenitors, that ultimately comprise the sympathetic nervous system.

That's because, Bronner says, researchers previously looked for evidence of sympathetic nervous system too early in lamprey development. In birds, for example, the sympathetic nervous system forms in the first two or three days of development, and many other vertebrates develop these cells early in gestation. But in lamprey, Edens and her team discovered that the neural crest–derived progenitor cells (those that will ultimately give rise to sympathetic neurons) only first appear as long as a month post-fertilization and do not fully mature into neurons until around four months, during the larval stage.

While it remains unknown whether the sympathetic nervous system of lamprey mediates fight-or-flight-like behaviors similar to those observed in other vertebrates, these findings suggest that the developmental program governing formation of sympathetic neurons is evolutionarily conserved across all vertebrates, from lamprey to mammals.

The paper is titled "Neural crest origin of sympathetic neurons at the dawn of vertebrates." In addition to Edens and Bronner, co-authors are postdoctoral scholar Jan Stundl and graduate student Hugo Urrutia. Funding was provided by the National Institutes of Health. Marianne Bronner is an affiliated faculty member with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.