Caenorhabditis elegans LET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells

The conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. In C. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is likely mediated largely by the junctional component DLG-1 discs large, which we demonstrate is also essential for directed outgrowth of the seam cells. Our data uncover multiple essential functions for LET-413 in larval development and show that the polarized outgrowth of the epithelial seam cells is controlled by LET-413 Scribble and DLG-1 Discs large.

Author summary Most cells in multicellular organisms are organized along a directional axis of cell polarity. One protein that is important for this polarized organization is the conserved polarity regulator Scribble. This protein has several functions, including forming the basolateral domains of cells, promoting the formation of cell junctions, and promoting cell migration. How Scribble performs these functions is not fully understood. In this paper we study the role of Scribble during larval development of the small nematode Caenorhabditis elegans using an inducible protein degradation system. We show that Scribble, called LET-413 in C. elegans, is essential in the epidermal epithelium for animal development, as depletion of LET-413 in only this tissue blocks growth. We also demonstrate that LET-413 is required for the polarized outgrowth of an epithelial cell type called the seam cells, a process resembling cell migration. Finally, we show that one major function of LET-413 in seam cell outgrowth is the localization of the junctional component Discs large (DLG-1), which we demonstrate is also essential for this process. Our data thus uncover multiple essential functions for LET-413 in larval development and provide new insights into how the directional outgrowth of epithelial seam cells is controlled.