Epithelial tube formation and elongation

Epithelial tubulogenesis is a fundamental process in the development of certain organs across metazoan. Tubes that are not formed properly whether transiently during embryogenesis, or permanently as an integral part of an organ, can cause birth defects and diseases, yet the mechanisms that determine tubule formation, size and shape are not fully understood.

The basic structure of epithelial tubes is a highly polarized epithelium surrounding a central luminal space. The apical surfaces face the lumen while the basal surfaces contact other tissues or a basement membrane.

The Caenorhabditis elegans excretory system has served as an excellent model for studying epithelial tube formation these past 40 years.  The function of the excretory system is in osmoregulation – the organ is responsible for collecting excess water and solutes throughout the body and secreting them outside through the pore cell. The system has many characteristics similar to other renal systems and other epithelial and endothelial tube networks that are found in different organisms.

It is a very simple tubular organ that consists of just three unicellular tubes (canal, duct, and pore) connected in tandem to form a continuous lumen. The excretory canal cell is H-shaped with four canals, two anterior canals that span the pharynx and two posterior canals spanning the length of the body, making it the largest single nucleus cell in the nematode.

The lumen and apical membrane of the canal is surrounded by actin filaments that are encased by 3 types of intermediate filaments; the structure is termed the Terminal Web. During tubulogenesis of the canal cell, in late embryos and the L1 stage, an actin rich structure is visible at the very edge of the canal.  This leading-edge F-actin is adjacent, but distinct from the apical F-actin around the lumen and is reminiscent of the growth cone in growing neuronal axons. Yet it is still not clear how the canal elongates along the entire body of the worm at the L1 stage and how it then maintains elongation during the different larval stages until adulthood, when the worm’s body continues to grow. We are interested in the regulation of the cytoskeletal components responsible for canal elongation and the forces that govern this process.