Academic journal article Genetics

Regulation of Axon Guidance by the Wnt Receptor Ror/CAM-1 in the PVT Guidepost Cell in Caenorhabditis Elegans

Academic journal article Genetics

Regulation of Axon Guidance by the Wnt Receptor Ror/CAM-1 in the PVT Guidepost Cell in Caenorhabditis Elegans

Article excerpt

IN humans or other bilaterally symmetric animals, the nervous system is divided into two mirror image halves that are separated by the midline. During the development of the nervous system, some axons do not cross the midline at all, while other axons cross the midline exactly once. The choice for axons to cross or not to cross the midline is dependent on the expression of specific receptors in the axons that recognize and bind to attractive or repulsive guidance cues provided by other cells (Tessier-Lavigne and Goodman 1996). In vertebrates, UNC-6/Netrin and Sonic Hedgehog can attract axons to grow toward the midline (Charron et al. 2003), while Slit and Semaphorins repel growth cones away from the midline (Zou et al. 2000). Slit repels cells and axons that express Robo receptors (Dickson 2002). In Drosophila, all neurons express robo, but axons that cross the midline do not have Robo at the cell surface (Kidd et al. 1998). The levels of Robo are regulated by Commissureless (Comm). When a neuron expresses Comm, it will form a complex with Robo that will be degraded in lysosomes. The axons of these neurons are then allowed to cross the midline (Keleman et al. 2002, 2005). When the axon has crossed the midline, the expression of comm is lost and Robo will reappear at the surface and prevent the axon from recrossing. Vertebrates lack a Comm ortholog; instead a divergent member of the Robo family, Robo3/Rig-1, prevents axons from responding to Slit without downregulating or degrading Robo receptors (Sabatier et al. 2004).

The Caenorhabditis elegans Robo receptor SAX-3 is involved in midline guidance and worms also lack a Comm ortholog. The kinesin-related protein VAB-8 regulates SAX-3 levels in neurons that migrate along the anterior/posterior axis (Levy-Strumpf and Culotti 2007; Watari-Goshima et al. 2007) but it is not known whether it also does so in axons that cross the midline.

The Wnt family of secreted glycoproteins regulate anterior/ posterior and dorsal/ventral guidance of cells and axons together with the Netrin pathway (Herman et al. 1995; Zecca et al. 1996; Rocheleau et al. 1997; Thorpe et al. 1997; Whangbo et al. 2000; Goldstein et al. 2006; Levy-Strumpf and Culotti 2014). There are 19 Wnts in humans, seven in Drosophila, and five in C. elegans that can signal through a canonical ß-catenin pathway, or via the planar cell polarity (PCP) or the Wnt/calcium pathways (Wodarz and Nusse 1998). Wnt signaling is also known to regulate axon crossing at the midline. In Drosophila, midline axons that express the Wnt receptor Derailed are repelled away from the posterior commissure due to the presence of Wnt5 (Yoshikawa et al. 2003). In addition, loss of the zebrafish homolog of the Wnt receptor Frizzled-3a (zfzd3a) or Wnt8b causes the expansion of slit-2 expression in the telencephalon and as a consequence, axons fail to cross the anterior midline of the brain (Hofmeister et al. 2012; Hofmeister and Key 2013).

In this study we show that Wnt signaling is involved in midline guidance of ventral nerve cord (VNC) axons in the nematode C. elegans. The C. elegans VNC consists of two asymmetric bundles of neurons and axons that are separated by the midline. The left side contains only four neurons (PVPR, PVQL, AVKR, and HSNL) and the right side contains >50 neurons (White et al. 1976). The first neuron that extends an axon on the right side is the pioneering AVG neuron. The remaining neurons on the right side follow in a specific order. The left side is pioneered by the PVPR interneuron, followed by the PVQL interneuron (Durbin 1987). The HSN motor neurons that control egg laying are the last neurons to send out their axons into the VNC during the L2L4 larval stages (Adler et al. 2006). Most axons in the VNC do not cross the midline and those that do, cross the midline only once, for example PVPL and PVPR that cross over posterior to the PVT neuron (Wadsworth and Hedgecock 1996). The nematode midline is a dynamic structure that during embryogenesis and early larval stages is composed of motor neuron cell bodies and in later larval stages and adults of a ridge of hypodermal cells (Hao etal. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.