The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

Abstract

The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal's life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes.KEYWORDS Caenorhabditis elegans; tubulogenesis; excretory-secretory system; WormBook

Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans

“…Cloned exc genes encode cytoskeletal proteins and proteins that anchor the terminal web to the apical membrane (Göbel et al 2004;Praitis et al 2005;Kolotuev et al 2013;Shaye and Greenwald 2015), regulate ionic and fluid movement in the canal lumen (Berry et al 2003;Liegeois et al 2007;Hisamoto et al 2008;Khan et al 2013), and regulate movement of messenger RNA (mRNA) and endosomes within the cell (Fujita et al 2003;Tong and Buechner 2008;Mattingly and Buechner 2011). Similar defects in single-cell tube maintenance have also been described for the C. elegans excretory duct cell (Stone et al 2009;Sundaram and Buechner 2016), which initially forms as an autocellular seamed cell whose lumen connects to the seamless excretory cell lumen (Nelson et al 1983).The EXC-5 guanine exchange factor (GEF) regulates endocytic recycling (Gao et al 2001;Mattingly and Buechner 2011). Alleles of exc-5 show epistatic effects on exc-9 mutants, which suggests that EXC-5 works downstream of the EXC-9 LIM-domain protein to regulate movement between early and recycling endosomes (Mattingly and Buechner 2011).…”

“…The mechanisms of maintenance of tube diameter as animals age and grow are still relatively unknown. Mechanosensitive channels on primary cilia projecting into the lumen regulate luminal diameter in multicellular tubes such as blood vessels, nephrons, and biliary ducts (Ware et al 2011;Martinac 2014), but narrower single-celled tubules such as those of myelinating Schwann cells do not express cilia on their luminal surface (Yoshimura and Takeda 2012).The C. elegans excretory canal cell provides a tractable genetic model for investigating maintenance of luminal diameter in a seamless single-celled tube (Buechner 2002;Sundaram and Buechner 2016). The excretory canal cell is born in midembryogenesis, forms a hollow lumen, and extends both leftward and rightward to the lateral surface, where each side branches and extends canals both anteriorward and posteriorward to form an "H"-shaped structure (Chitwood and Chitwood 1974;Sulston et al 1983) ( Figure 1A).…”

A network of conserved formins, regulated by the guanine exchange factor EXC-5 and the GTPase CDC-42, modulates tubulogenesis in vivo

“…This protocol was followed for both single and compound mutants. We note that by using this protocol we are interfering with CYK-1 function both during the embryonic/early larval 'active' EC outgrowth phase, and during the later larval 'passive' outgrowth phase (Sundaram and Buechner, 2016). Therefore, any defects seen may reflect disruption of either, or both, these stages of EC outgrowth.…”

“…During the first larval stage, the canals actively grow until they span almost the entire length of the animal: the anterior canals terminate prior to reaching the buccal cavity, and the posterior canals typically terminate at or near the rectum. Thereafter, the canals continue to grow passively to keep up with the lengthening body (Sundaram and Buechner, 2016; Fig. 1A,G; Fig.…”

“…The EC is a tractable model to study the genetic control of tubulogenesis (Sundaram and Buechner, 2016). Several conserved regulators of tubulogenesis were identified in a pioneering screen for mutations that resulted in cystic excretory cell canals (Buechner et al, 1999).…”