ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C-elegans

The C. elegans epidermis is a simple epithelium comprised of three major ce ll types, the seam, syncytial and P cells. While specification of all major epidermal cells is known to require the ELT-1 GATA transcription factor, l ittle is known about how the individual epidermal cell types are specified. We report that elt-5 and -6, adjacent genes encoding GATA factors, are ess ential for the development of the lateral epidermal cells, the seam cells. Inhibition of elt-5 and -6 function by RNA-mediated interference results in penetrant late embryonic and early larval lethality. Seam cells in affecte d animals do not differentiate properly: the alae, seam-specific cuticular structures, are generally absent and expression of several seam-specific ma rkers is blocked. In addition, elt-3, which encodes another GATA factor nor mally expressed in non-seam epidermis, is often ectopically expressed in th e seam cells of affected animals, demonstrating that ELT-5 and -6 repress e lt-3 expression in wild-type seam cells. Seam cells in affected animals oft en undergo inappropriate fusion with the epidermal syncytia. interference o f elt-5 and -6 function during larval development can cause fusion of all s eam cells with the surrounding syncytia and pronounced defects in molting. elt-5 and -6 are both expressed in seam cells and many other cells, and are apparently functionally interchangeable. Their expression is controlled by separable tissue-specific regulatory elements and the apportionment of mon ocistronic versus dicistronic transcription of both genes appears to be sub ject to cell-type-specific regulation. Collectively, these findings indicat e that elt-5 and -6 function continuously throughout C. elegans development to regulate seam cell differentiation and cell fusion.