Riding the neural crest
Studies that track cell migration, fate illuminate gut disorders
During the fourth week of human embryonic development, in the ridges of the closing neural tube, a remarkable group of cells emerges.
Named for their birthplace, these “neural crest” cells journey to sites near and far in the developing embryo, where they form a wide array of tissues, including the peripheral nervous system, facial skeleton and melanocytes in the skin.
The fate of an individual neural crest cell – what it becomes – relates to both its starting position (top-to-bottom) along the neural tube and to its migration path, explains Michelle Southard-Smith, Ph.D.
She’s interested in the cells that trek from the neural tube ridges into the future gut and along the length of the developing intestine. There, they form the neurons and glia of the enteric nervous system – the “brain” of the gut that controls motility, mucosal transport, tissue defense and vascular perfusion of the gastrointestinal tract.
“These cells have the longest neural crest migration that occurs in the developing embryo,” says Southard-Smith, assistant professor of Medicine and Cell & Developmental Biology at Vanderbilt. “Variations that impair the ability of those neural crest cells to complete the migration or to survive and become functional neurons and glia in the gut wall can cause gastrointestinal disorders like Hirschsprung’s disease.”
Patients with Hirschsprung’s disease are missing enteric ganglia (nerve bundles) in the intestine, causing constipation and blockages and requiring surgical intervention. Hirschsprung’s occurs in one out of every 5,000 live births in the United States and can be fatal.
The severity of the disease depends on how much of the large intestine is affected – how successful, or not, the neural crest cells were in migrating through and populating the gut, Southard-Smith explains.
Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.
Following the glowing cells with imaging technologies has already revealed a surprise: differences between neurons and glia are evident when the neural crest cells are just starting their journey to the gut, suggesting that cells make fate decisions earlier than scientists believed, Southard-Smith says.
In addition to tracking cells as they migrate, the researchers are capturing the glowing cells and culturing them in the laboratory. The aim is to understand how the cells respond to various growth factors and to evaluate their ability to form enteric nerves and glia after transplantation into a mouse model of Hirschsprung’s disease.
Ultimately, the research could offer treatment options for patients with the disease, Southard-Smith says.
“There are neural crest cells in skin – we’re hoping to take them out and reprogram them with cues to make them become enteric neurons and glia,” she says. “That’s where we’re going with this.”
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