The VAB-1 Eph receptor tyrosine kinase and SAX-3/Robo neuronal receptors function together duringC. elegansembryonic morphogenesis

Abstract

Mutations that affect the single C. elegans Eph receptor tyrosine kinase VAB-1 cause defects in cell movements during embryogenesis. Here, we provide genetic and molecular evidence that the VAB-1 Eph receptor functions with another neuronal receptor, SAX-3/Robo, for proper embryogenesis. Our analysis of sax-3 mutants shows that SAX-3/Robo functions with the VAB-1 Eph receptor for gastrulation cleft closure and ventral epidermal enclosure. In addition, SAX-3 functions autonomously for epidermal morphogenesis independently of VAB-1. A double-mutant combination between vab-1 and slt-1 unmasks a role for the SLT-1 ligand in embryogenesis. We provide evidence for a physical interaction between the VAB-1 tyrosine kinase domain and the juxtamembrane and CC1 region of the SAX-3/Robo receptor. Gene dosage, non-allelic non-complementation experiments and co-localization of the two receptors are consistent with a model in which these two receptors form a complex and function together during embryogenesis.

Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

“…We chose to further examine SAX-3 and obtained the strain sax-3(ky123); quEx168 [psax-3::sax-3::gfp; odr-1::RFP] (Ian Chin-Sang, Queen's University, Kingston, ON, Canada), which has the ability to rescue sax-3(ky123) and resembles the true endogenous expression pattern (Ghenea et al 2005). To determine whether SAX-3 can rescue canal extension defects under control of its endogenous promoter, this strain was crossed into unc-53(n166); sax-3(ky123) double null mutants, as sax-3 single mutants do not display posterior canal truncation.…”

“…Another possibility is that SAX-3 may function with a coreceptor to specify attraction to Slit within the excretory cell. For example, SAX-3 is known to physically interact with the VAB-1 Eph receptor during embryogensis, while EVA-1 physically interacts with SAX-3 to provide cell specificity to the activation of SAX-3 signaling by SLT-1 in the AVM and PVM neurons (Ghenea et al 2005;Fujisawa et al 2007). …”

“…SAX-3 may function with a coreceptor to specify attraction to Slit within the excretory cell, and our data are consistent with EVA-1 being the potential SAX-3 coreceptor. There are other examples of SAX-3 functioning with a coreceptor to specify receptor function: SAX-3 is known to physically interact with the VAB-1 Eph receptor during embryogensis, while EVA-1 physically interacts with SAX-3 to provide cell specificity to the activation of SAX-3 signaling by SLT-1 in the AVM and PVM neurons (Ghenea et al 2005;Fujisawa et al 2007). Already known for being involved in DV guidance, our findings confirm a role for SLT-1, SAX-3/ROBO, and EVA-1 in AP migration of the excretory cell.…”

Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans

“…The ephrin pathway does not seem to play an important role during the development of either neuron: a mutation in the only known ephrin receptor in C. elegans, vab-1 (George et al, 1998;Ghenea et al, 2005), has no effect on the NSM or M2 neurons.…”

The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1

“…The nematode Caenorhabditis elegans has proven to be an excellent model organism for the elucidation of global guidance mechanisms controlling migration. Several signals and receptors reported to control cell migration in vertebrates have been described in C. elegans, including: UNC-6/netrin and its receptors UNC-40/DCC and UNC-5 (Hedgecock et al, 1990;Ishii et al, 1992), the SLT-1/SLIT cue (Hao et al, 2001) and its multifunctional receptor SAX-3/ROBO (Ghenea et al, 2005;Levy-Strumpf and Culotti, 2007;Zallen et al, 1998), WNTs and their associated FZ receptors (Pan et al, 2006), and growth factors such as EGL-17/FGF (Burdine et al, 1997) and its receptor EGL-15/FGFR (Birnbaum et al, 2005;Bulow et al, 2004;DeVore et al, 1995). Besides the identification of the signaling cues and their receptors, the machinery required for the subcellular positioning of receptors is also being uncovered.…”