Lethal congenital contracture syndrome 1 (LCCS1) is a prenatally fatal, autosomal recessive human disorder. Affected foetuses have multiple defects, including limb deformities (contractures), loss of voluntary muscle movement and a distinct neuropathology. Mutations in GLE1, which encodes a protein involved in mRNA export and translation, have been implicated in LCCS1 and, on , Susan Wente and co-workers investigate the link between Gle1 function and LCCS1 pathology using zebrafish as a model system. They report that disruption of Gle1 function produces phenotypes in zebrafish embryos that parallel those of human LCCS1 foetuses, including a reduction of motoneurons and aberrant arborization of motor axons. Surprisingly, the researchers report, apoptosis of neural precursors, rather than degeneration of differentiated neurons, as previously suggested, causes the motoneuron deficiency. The researchers propose, therefore, that rapidly dividing cells, including organ precursors in both neuronal and non-neuronal tissue, have a high demand for Gle1 activity, and that apoptosis of these precursors because of Gle1 deficiency produces the pleiotropic abnormalities seen in LCCS1 foetuses.
