Regulation of the proliferation and differentiation of the stem cell-like seam cell lineages.

Abstract

We used the development of the stem-cell like seam cells as a model to study how the cell proliferation and differentiating during development are elaborately controlled. At each of the four larval stages, the seam cells undergo asymmetric division, with one daughter cell fusing with the hypodermal syncytium, hyp7, and the other daughter cell retaining seam cell fate. At the L2 larval stage, seam cells H1, V1-V4 and V6 also undergo one round of symmetric division with both daughter cells maintaining seam cell fate. This division pattern is referred to as proliferative seam cell division. As a result, the number of seam cells increases from 10 at the hatching stage to 16 from the L2 larval stage and beyond. At the L4 larval-to-adult switch, the seam cells terminally differentiate, which involves in the cessation of cell division, fusion of cells and synthesis of adult culticular structures, called alae. In order to study how the seam cell division and differentiation is regulated, we performed a genetic screen to identify mutants with increased or reduced number of seam cells at adult stage. From 4,000 genomes screened, we have identified several mutants. One of the mutants appears to be ceh-16, encoding the only C. elegans ortholog of engrailed gene, which is highly conserved from worm to human. Mutations in ceh-16 lead to a decreased number of seam cells due to the defects in the proliferative seam cell proliferation. We are investigating how ceh-16 regulates the seam cell division and what the relationships between ceh-16 and other genes, such as rnt-1, that also has a role in seam cell division. One of the human engrailed homologues EN2 is reported to enhance cell proliferation and prevent differentiation of epithelial cells (Martin et al., 2005). Thus, our studies will provide insight in the role of engrailed in regulation of cell proliferation and differentiation.