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Unformatted text preview: 3679 Introduction Cell movements are crucial for the development of all embryos. If cells are not correctly positioned in the developing embryo, tissues or organs may not be formed or they may be formed in the wrong place or at the wrong time. Cells can navigate to their correct position by sensing their environment for positional cues. In C. elegans , the VAB-1 Eph receptor tyrosine kinase and its ephrin ligand EFN-1 function primarily as guidance cues on neuroblasts for proper neuronal and epidermal cell movements (Chin-Sang et al., 1999; George et al., 1998). The vertebrate Eph receptor tyrosine kinases (RTKs) and their ligands, the ephrins, have diverse roles during development. These include axon guidance, angiogenesis and the regulation of cancer (reviewed by Adams and Klein, 2000; Dodelet and Pasquale, 2000; Drescher, 2000; Flanagan and Vanderhaeghen, 1998; Kullander and Klein, 2002). Understanding how the vertebrate Eph receptors signal during development is under intense research, but the large number of receptors and ephrin ligands, as well as the promiscuity of their binding partners, can complicate the picture. By contrast, C. elegans has only one Eph RTK and four ephrin ligands. Null mutations in either the vab-1 Eph RTK or efn-1 ephrin result in defective cell movements, and, as a result, the embryos usually die or have severe morphogenesis defects (Chin-Sang et al., 1999; George et al., 1998). However, the fact that the penetrance of the lethality is not complete suggests that there is genetic redundancy in C. elegans Eph RTK signaling, that is, other signaling pathways may work together or in parallel with the VAB-1 Eph RTK. Indeed a divergent ephrin, EFN-4, and a leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase (RPTP), PTP-3, work redundantly, or in parallel, with the VAB-1 Eph RTK (Chin- Sang et al., 2002; Harrington et al., 2002). We report that the VAB-1 Eph RTK shows a dosage- dependent genetic interaction with the conserved axon guidance receptor, SAX-3/Robo. The Roundabout (Robo) family of receptors are evolutionary conserved and have been implicated in mediating axon guidance events, specifically axon repulsion upon binding its ligand Slit (Brose et al., 1999; Challa et al., 2001; Kidd et al., 1998; Lee et al., 2001; Seeger et al., 1993; Zallen et al., 1998) (for a review, see Wong et al., 2002). Like the vertebrate and Drosophila counterparts, the C. elegans Robo homolog SAX-3 is required for multiple axon guidance events, including midline crossing, ventral guidance and nerve ring positioning (Zallen et al., 1999; Zallen et al., 1998). However, the role of SAX-3 in early embryonic cell movements has not been described. Four-dimensional video microscopy revealed that sax-3 embryos display defects in neuroblast gastrulation cleft closure, as well as ventral movements of the epidermal cells, during ventral closure, similar to those observed in the vab-1 (Eph RTK) and efn-1 (Ephrin) mutants. sax-3...
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This note was uploaded on 12/06/2011 for the course BIOL 430 taught by Professor Dr.ianchin-sang during the Winter '10 term at Queens University.
- Winter '10