The Caenorhabditis elegans orthologue of the human gene responsible for spinal muscular atrophy is a maternal product critical for germline maturation and embryonic viability

Spinal muscular atrophy (SMA) is a common disorder characterized by loss of lower motor neurones of the spinal cord. The disease is caused by mutation s in the survival motor neurone (SMN) gene, SMN is ubiquitously expressed a nd evolutionarily conserved, and its role in RNA processing has been well e stablished, However, these properties do not explain the observed specifici ty of motor neurone death, To gain further insight into the function of SMN , we have isolated and characterized the Caenorhabditis elegans orthologue of the SMN gene (CeSMN), Here we show that CeSMN is transmitted maternally as a predominantly nuclear factor, which remains present in all the blastom eres throughout embryonic development and onwards into adulthood. In adult nematodes, a CeSMN-green fluorescent protein fusion protein is expressed in a number of cell types including the germline, Both disruption of the endo genous CeSMN function and overexpression of the gene result in a severe dec rease in the number of progeny and in locomotive defects, In addition, its transient knockdown leads to sterility caused by a defect in germ cell matu ration. The expression pattern and functional properties so far observed fo r CeSMN, together with its unusual behaviour in the germline, indicate that SMN may be involved in specific gene expression events at these very early developmental stages, We have also identified a deletion in the CeSMN prom oter region in egl-32, This mutant may become a useful genetic tool with wh ich to explore regulation of CeSMN and hence provide possible clues for nov el therapeutic strategies for SMA.