The ortholog of the human proto-oncogene ROS1 is required for epithelial development in C. elegans.
Bottom Line: Little is known about the role of ROS1, however in vertebrates it has been implicated in promoting differentiation programs in specialized epithelial tissues.We also provide evidence of a direct relationship between ROL-3, the mucin SRAP-1, and BCC-1, the homolog of mRNA regulating protein Bicaudal-C.This study answers a longstanding question as to the developmental function of ROL-3, identifies three new genes that are expressed and function in the developing epithelium of C. elegans, and introduces the nematode as a potentially powerful model system for investigating the increasingly important, yet poorly understood, human oncogene ROS1.
Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. email@example.comShow MeSH
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Mentions: The molting defects associated with rol-3 alleles might be due to the inability to release an improperly formed cuticle. Molting defects are also often associated with mutations that lead to the disruption of seam cell morphology (Brooks et al., 2003; Silhankova et al., 2005; Ruaud and Bessereau, 2006; Meli et al., 2010; Monsalve et al., 2011; Singh et al., 2011). Our examination of COL-19::GFP expression in rol-3(s1040ts) adult animals revealed the presence of defects in the patterning of the alae, the formation of which are dependent on the structure of the underlying seam syncytium (Page and Johnstone, 2007; and reviewed by Altun and Hall, 2009a2009b). This indicated that formation of seam syncytium might be compromised in these animals. To observe the developing seam syncytium we utilized the transgenic array wIs78, which expresses GFP in seam cell nuclei and adherin junctions (Li et al., 2005). In rol-3(s1040ts) and rol-3(e754) larvae raised at permissive temperature seam cell elongation progresses normally or with minor defects in seam cell contact (Fig. 4b and Supporting Information Fig. S1e). Adult animals develop a seam syncytium that can be mildly disorganized, bifurcated and/or discontinuous (Fig. 4d, Supporting Information Fig. S1f and Table2). The specification of seam cell identity is not significantly affected in rol-3(s1040) animals, based on the number of seam cells displaying robust expression of SCM::GFP (Fig. 4d and Table2). However, rol-3(s1040ts) animals arrested at the restrictive temperature of 20° exhibit severe defects in seam formation, with many cells failing to elongate correctly (Fig. 4d/e and Table2). All animals observed present with these defects, though the severity of the phenotype varies from those that complete cell contact in all but a few cells, to those where cell contact fails completely (Table2). In animals homozygous for the allele rol-3(s126), seam cells completely fail to elongate toward one another, retaining a rounded appearance (Fig. 4g/f). Additionally, seam cell number appears to be reduced in both rol-3(s1040) and rol-3(s126) animals (Fig. 4d, g).
Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. firstname.lastname@example.org