Analysis of Caenorhabditis elegans vulval morphogenesis reveals novel mechanisms for initiation and maintenance of biological tubes .

摘要

The formation of biological tubes is common to the development of all metazoans. A simple model for studying all aspects of this complicated developmental process is the C. elegans vulva. This simple epithelial tube consists of seven toroidal-shaped cells surrounding a central lumen. Using this model, I have uncovered novel mechanisms in lumen initiation and lumen maintenance during vulval tubulogenesis. I have shown that the putative palmitoyltransferase EGL-26, belonging to the NlpC/P60 family of enzymes, is specifically required late in dorsal vulval morphogenesis. Moreover, I have shown that mutation of egl-26 results in a collapse of the dorsal vulval lumen. I also show that the conserved catalytic residues of EGL-26 are required for function in vivo, providing the first example of a function for this family of proteins in metazoan development. In addition, I have closely analyzed the role of the gonadal anchor cell in vulval morphogenesis. Using several mutants, I have shown that invasion of the vulva epithelium by the anchor cell is required for initiation of the dorsal vulval lumen. In cases where the anchor cell does not invade properly, no dorsal lumen is formed. I have confirmed that this effect is specific to morphogenesis and not due to fate or polarity defects. This work leads to a model of vulval tubulogenesis that requires the anchor cell to initiate dorsal lumen formation and EGL-26 function to maintain the lumenal structure, suggesting that initiation and maintenance are controlled separately. An understanding of these mechanisms in the C. elegans vulva will likely lead to insight into potentially conserved mechanisms in higher eukaryotes.