Thalidomide-induced limb abnormalities may reflect a 'precursor' rather than a 'patterning' problem, a Nature study suggests. The study, which forces a rethink of a prominent limb development model, suggests a previously unappreciated cause for phocomelia birth defects.
Phocomelia, a rare, devastating, congenital limb malformation in which long bones are shortened, has been presumed to be a patterning disorder in which genes related to body layout go off-kilter. But Clifford Tabin and colleagues use a chick limb bud X-irradiation model to show that the disorder arises, not from a patterning defect, but from the loss of skeletal progenitor cells.
The demonstration that 'shoulder-to-finger' patterning is unaffected by X-irradiation challenges a classic theory of limb development. Past studies of X-irradiation-induced phocomelia provided corroborative evidence for the progress zone model of development, whereby cell identity is determined by the time spent at the apex of the limb bud or 'progress zone'. However, the current results are the latest in a series that contradict this model.
Clifford Tabin (Harvard Medical School, Boston, MA, USA)
Abstract available online.
(C) Nature press release.
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