A group led by Joseph Gleeson at UC San Diego and Xiaoxu Yang at the University of Utah reported in Nature on April 1 that neural crest cells — the embryonic population that gives rise to peripheral neurons, pigment and much of the face — commit to adult identity earlier than forty years of textbook work has said. [1] The paper uses CRISPR-based lineage tracing in mouse embryos and finds the fate bias separating sensory-ganglion neurons from sympathetic ones emerges inside the neural tube, before delamination. The received model had these decisions made during or after migration, with a long multipotent window.

The method matters. Gleeson's group introduced large numbers of neutral genetic barcodes via CRISPR editing into the embryo, then read the barcodes out of adult sensory and sympathetic ganglia. [1] If the cells had been multipotent at delamination, the same barcodes should have appeared in both destinations. They did not. The two ganglia types shared rostrocaudal axial spread but very little clonal overlap. The fate choice was already made.

The clinical tail is neuroblastoma and related childhood cancers — cancers of sympathetic-lineage neural crest derivatives that kill children whose tumors lock into aggressive profiles for reasons imperfectly understood. If fate bias is set weeks earlier than the field assumed, the window in which a cell can be pushed toward the wrong identity is earlier too. That changes where researchers look for the failure. A March Nature Reviews Molecular Cell Biology review had already begun sketching the updated gene regulatory networks the result fits. [2]

The paper uses mouse embryos; the human extrapolation is not automatic. Neuroscience News quoted Gleeson naming that caveat himself. [3] A competing line of work has argued the opposite for years. The back-and-forth will run for several Natures.

-- KENJI NAKAMURA, Tokyo