PASADENA, Calif.—There's a time soon after conception when the stem cells in a tiny area of the embryo called the neural crest are working overtime to build such structures as the dorsal root ganglia, various neurons of the nervous system, and the bones and cartilage of the skull. If things go wrong at this stage, deformities such as cleft palates can occur.
In an article in this week's issue of Nature, a team of biologists from the California Institute of Technology announce that they have determined that neural crest precursors can be identified at surprisingly early stages of development. The work could lead to better understanding of molecular mechanisms in embryonic development that could, in turn, lead to therapeutic interventions when prenatal development goes wrong.
According to Marianne Bronner-Fraser, the Ruddock Professor of Biology at Caltech, the findings provide new information about how stem cells eventually form many and diverse cell types in humans and other vertebrates.
"We've always assumed that the precursor cells that form the neural crest arise at a time when the presumptive brain and spinal cord are first visible," she says. "But our work shows that these cells arise much earlier in development than previously thought, and well before overt signs of the other neural structures.
"We also show that a DNA binding protein called Pax7 is essential for formation of the neural crest, since removal of this protein results in absence of neural crest cells."
The work involves chicken embryos, which are especially amenable to the advanced imaging techniques utilized at Caltech's Biological Imaging Center. The results showed that interfering with the Pax7 protein also interfered with normal neural crest development.
"Because neural crest cells are a type of stem cell able to form cell types as diverse as neurons and pigment cells, understanding the molecular mechanisms underlying their formation may lead to therapeutic means of generating these precursors," Bronner-Fraser explains. "It may also help treat diseases of neural crest derivatives, like melanocytes, that can become cancerous in the form of melanoma."
The work was funded by the NIH and performed at Caltech by Martin Garcia-Castro, a former postdoctoral researcher who is currently an assistant professor at Yale University, and Martin Basch, a former Caltech graduate student who is currently a postdoctoral fellow at the House Ear Institute.
The paper appears in the May 11 issue of Nature. The title of the article is "Specification of the neural crest occurs during gastrulation and requires Pax7."
