Epithelial tubes are fundamental building blocks of complex organs, but their molecular and architectural requirements are not well understood1,2. C. elegans is particularly well suited to study tubulogenesis since three of its major tubular organs are formed by different types of single-layered epithelia. We previously reported the preferential expression of
erm-1 (the C. elegans ortholog of the ezrin-radixin-moesin cytoskeleton-membrane linker family) and
nfm-1 (the worm Neurofibromatosis II ortholog) in apical versus basolateral tubular epithelia.
erm-1 is expressed and functions at the luminal membranes of the intestine, excretory canal, and gonad, all epithelia not stabilized by cuticle. Here we report further confirmation that
erm-1 affects apical membrane modeling in an apparently polarity- and junction-independent fashion. We present serial section ultrastructural analysis data throughout the development of
erm-1(RNAi) embryos and larvae, revealing deterioration of the luminal scaffold both in the presence of normal cell junctions and in epithelia which lack junctions altogether. Defective apical membrane modeling interferes with epithelial rearrangement and tube extension, resulting in shape distortion of the lumen, surface twisting, and development of luminal cysts. Membrane and junction determinants, such as AJM-1, PAR-3, PKC-3 and others, appear only secondarily affected. We also identify a novel type of autophagic programmed cell death (PCD) in the intestine of
erm-1(RNAi) animals, which occurs proportionally to the cell shape and tissue architecture distortion, and appears to be at least partially
ced-3/ced-4-independent. We propose that
erm-1 is a predominantly structural molecule required to physically affix the expanding luminal membrane to the cortical cytoskeleton, a function essential to epithelia directly apposing a cell-free space (such as a lumen). The possible role of PCD in tube-specific epithelial morphogenesis will be discussed. References 1. Lubarsky, B. & Krasnow, M. A. Tube morphogenesis: making and shaping biological tubes. Cell 112, 19-28 (2003). 2. Buechner, M. Tubes and the single C. elegans excretory cell. Trends Cell Biol 12, 479-84 (2002).