Crest-fallen
How do neural crest cells maintain their biological identity?
As an embryo develops, different genetic programs become activated to give cell populations a specific biological identity that will shape their fate. For instance, when certain sets of genes get switched on, cells from the outermost layer of the embryo start to migrate to their final destination within the body. There, these ‘neural crest cells’ will contribute to bones and cartilage in the face, pigmented skin spots, and muscles or nerves in the gut.
When genes responsible for the neural crest identity are active, their instructions are copied into an ‘RNA molecule’ which will then relay this information to protein-building structures. How well the RNA can pass on the message depends on how long it persists within the cell. Certain RNA-binding proteins can control this process, but it is unclear whether and how this regulation takes place in neural crest cells. In their work, Hutchins et al. therefore focused on identifying RNA-binding proteins involved in neural crest identity.
Exploratory searches of genetic data from chick embryos revealed that, even before they started to migrate, neural crest cells which have recently acquired their identity produced large amounts of the RNA-binding protein Elavl1. In addition, these cells did not behave normally when embryos were deprived of the protein: they left the outer layer too soon and then switched off genes important for their identity. Genetic studies of neural crest cells lacking Elavl1 revealed that this effect was due to having lost the RNA molecule produced from the Draxin gene.
Introducing an additional source of Draxin into mutant embryos missing Elavl1 was enough to restore normal neural crest behaviour. Further biochemical experiments then showed that the RNA for Draxin decayed quickly in the absence of Elavl1. This suggests that the protein normally allows Draxin’s RNA to persist long enough to pass on its message.
These results reveal a new mechanism controlling the identity and behaviour of the neural crest. Since many cancers in adulthood arise from the descendants of neural crest cells, Hutchins et al. hope that this knowledge could lead to improved therapies in the future.
Originally published at https://elifesciences.org/digests/63600.
