A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning

Jenna L. Galloway, Irene Delgado, Maria A. Ros and Clifford J. Tabin ()
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Jenna L. Galloway: Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Irene Delgado: Universidad de Cantabria
Maria A. Ros: Instituto de Biomedicina y Biotecnología de Cantabria (CSIC-UC-IDICAN), C/ Herrera Oria s/n, 39011 Santander, Spain
Clifford J. Tabin: Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

Nature, 2009, vol. 460, issue 7253, 400-404

Abstract: A rethink on phocomelia The congenital disorder phocomelia is a rare limb malformation that became more familiar in the 1960s as a side effect of the use thalidomide in pregnancy. Phocomelia is mimicked in developing chick limb buds exposed to X-irradiation, and studies of the chick model provided important evidence for the long-established progress zone model of limb development, in which fibroblast growth factor produced by the apical ectoderm ridge directs cell fate. New work, involving molecular analysis and lineage tracing, shows that X-irradiation-induced phocomelia is not a patterning defect as was thought, but results from a time-dependent loss of skeletal progenitors. This finding challenges the current model of phocomelia aetiology as well as the predictions of the progress zone model.

Date: 2009
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DOI: 10.1038/nature08117

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