Nuclear gems and cajal (coiled) bodies in fetal tissues: Nucleolar distribution of the spinal muscular atrophy protein, SMN

SMN, the affected protein in spinal muscular atrophy (SMA), is a cytoplasmi c protein that also occurs in nuclear structures called "gems" and is invol ved in snRNP maturation. Coilin-p80 is a marker protein for nuclear Cajal b odies (coiled bodies; CBs) which are also involved in snRNP maturation, sto rage or transport. We now show that gems and CBs are present, in all fetal tissues, even those that lack gems/CBs in the adult. Most gems and CBs occu r as separate nuclear structures in fetal tissues, but their colocalization increases with fetal age and is almost complete in the adult. In adult tis sues, up to half of all gems/CBs are inside the nucleolus, whereas in cultu red cells they are almost exclusively nucleoplasmic. The nucleolar SMN is o ften more diffusely distributed, compared with nucleoplasmic gems. Up to 30 % of cells in fetal tissues have SMN distributed throughout the nucleolus, instead of farming gems in the nucleoplasm. The results suggest a function for gems distinct from Cajal bodies in fetal nuclei and a nucleolar functio n for SMN. Spinal cord, the affected tissue in SMA, behaves differently in several respects. In both fetal and adult motor neurons, many gems/CBs occu r as larger bodies closely associated with the nucleolar perimeter. Uniquel y in motor neurons, gems/CBs are more numerous in adult than in fetal stage s and colocalization of gems and CBs occurs earlier in development. These u nusual features of motor neurons may relate to their special sensitivity to reduced SMN levels in SMA patients. (C) 2001 Academic Press.