"It is somewhat counterintuitive that this kind of shutting off of genes is essential for promoting neural crest cell fate," she says. "Embryonic development often involves switches in the types of inputs that a cell receives. This is an example of a case where a negative factor must be turned offessentially a double negativein order to achieve a positive outcome."
Bronner says it was also surprising to see that an enzyme like DNMT has such a specific function at a specific time. DNMTs are sometimes thought to act in every cell, she says, yet the researchers have discovered a function for this enzyme that is exquisitely controlled in space and time.
"It is amazing how an enzyme, at a given time point during development, can play such a specific role of making a key developmental decision within the embryo," says Na Hu, a graduate student in Bronner's lab and lead author of the paper. "Our findings can be applied to stem cell therapy, by giving clues about how to engineer other cell types or stem cells to become neural crest cells."
Bronner points out that their work relates to the discovery, which won a recent Nobel Prize in Medicine or Physiology, that it is possible to "reprogram" cells taken from adult tissue. These induced pluripotent stem (iPS) cells are similar to embryonic stem cells, and many investigators are attempting to define the conditions needed for them to differentiate into particular cell types, including neural crest derivatives.
"Our results showing that DNMT is important for converting CNS cells to neural crest cells will be useful in defining the steps needed to reprogram such iPS cells," she says. "The iPS cells may in turn be useful for repair in human diseases such as familial dysautonomia, a disease in which there is depletion of autonomic and sensory neurons that are neural crestderived; for repair of jaw bones lost in osteo
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California Institute of Technology