| Summary: | 博士 === 國立臺灣大學 === 生物科技研究所 === 102 === Survival motor neuron (SMN) is a protein involved in the functions in assembly of snRNPs, transcriptional regulation and cellular trafficking. SMN gene is highly conserved across widely diverse species over biological kingdoms. Mutations in the SMN1 gene cause spinal muscular atrophy (SMA), an autosomal recessive disease and the most common genetic cause of childhood mortality. The incidence of SMA is approximately 1/6000-1/10,000 every live birth, and there are about 25 affected infants every year in Taiwan. In the most severe type, the consequences of SMA often reveal motor neuron loss, muscle degeneration and death. In a Drosophila model, it has been found that SMN expresses abundantly in stem cells and reaches its lowest level in differentiated cells. Deficiency of SMN leads to growth delay and rapid differentiation, indicating that SMN correlates to stem cell division, proliferation and differentiation. However, it is unclear whether a similar effect exists in vertebrates. Using mouse model, the results show that SMN is enriched in the inner cell mass of late blastocyst, embryonic stem cells (ESCs) and germline cells. Reduction of SMN impairs the pluripotent gene expression in ESCs, such as Sox2, Klf4 and Sall4. Moreover, it is found that the reduction of SMN activates ERK signaling and affects neuronal differentiation in vitro. Reduced SMN delays the cell growth and shows weaker signals of neuronal stem cell markers, like PAX6 and NESTIN, compared to those with a normal level of SMN. Over-expression of SMN provides protective effect for ESCs from retinoic acid-induced differentiation and stimulates neurite formation in in vitro differentiation. On the other hand, SMN also expresses abundantly in mouse germline cells, particularly in spermatocyte and growing oocyte. SMN is enriched in some spermatogonia stem cells, implying the loss of SMN might affect stem cell growth. In SMA model mice, the growth of gonadal tissues is decreased and the expression of spermatogonium marker is also down-regulated. More atretic follicles appear in the ovaries of female SMA mice. Taken together, our results suggest that SMN plays a role in the maintenance of stem cells, including pluripotent ESCs, neuronal progenitor, and male germline stem cells in mice.
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