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The ortholog of the human proto-oncogene ROS1 is required for epithelial development in C. elegans.

Jones MR, Rose AM, Baillie DL - Genesis (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. jonesmr@mail.ubc.ca

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Development of the seam syncytium is perturbed in animals carrying mutations in rol-3. a. Wild type L2 stage animal showing the characteristic ladder structure of the seam cells. b. rol-3(s1040ts) L2 animal raised a permissive temperature displaying a superficially wild type seam structure. c. WT adult seam syncytium is narrow and complete (arrow). d. Adult rol-3(s1040ts) animal displaying a disordered seam that is bifurcated (arrowheads). e. Arrested rol-3(s1040ts) animal. Two seam cells have elongated correctly (arrowhead) while an adjacent SCM::GFP expressing seam cell has ectopically fused with the hypodermis (arrow). A seam cell that has lost SCM::GFP expression and not elongated can be seen (asterisk). Several seam cells in the anterior of the animal have lost SCM::GFP expression and fused with the hypodermis (left image). f. Arrested rol-3(s126) animal showing a reduced number of AJM-1::GFP positive seam cells that have not elongated, note: several seam cells are not in the focal plane in this image (arrowheads). g. WT L3 animal expressing seam specific elt-5::mCherry. h. Arrested rol-3(s1040ts) animal with an L3 equivalent number of divided elt-5::mCherry positive cells. Note that the animal is much smaller than wildtype. Several cells of the V lineage have lost of elt-5::mCherry expression (asterisks). i. rol-3(tm3908) animal arrested approximately at the L3 stage showing severe loss of elt-5::mCherry specification in the V lineage J. Quantification of the loss of seam cell specification in the H, V and T seam cell lineages in arrested rol-3(tm3908) animals. Scale bars, 25μm.
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fig04: Development of the seam syncytium is perturbed in animals carrying mutations in rol-3. a. Wild type L2 stage animal showing the characteristic ladder structure of the seam cells. b. rol-3(s1040ts) L2 animal raised a permissive temperature displaying a superficially wild type seam structure. c. WT adult seam syncytium is narrow and complete (arrow). d. Adult rol-3(s1040ts) animal displaying a disordered seam that is bifurcated (arrowheads). e. Arrested rol-3(s1040ts) animal. Two seam cells have elongated correctly (arrowhead) while an adjacent SCM::GFP expressing seam cell has ectopically fused with the hypodermis (arrow). A seam cell that has lost SCM::GFP expression and not elongated can be seen (asterisk). Several seam cells in the anterior of the animal have lost SCM::GFP expression and fused with the hypodermis (left image). f. Arrested rol-3(s126) animal showing a reduced number of AJM-1::GFP positive seam cells that have not elongated, note: several seam cells are not in the focal plane in this image (arrowheads). g. WT L3 animal expressing seam specific elt-5::mCherry. h. Arrested rol-3(s1040ts) animal with an L3 equivalent number of divided elt-5::mCherry positive cells. Note that the animal is much smaller than wildtype. Several cells of the V lineage have lost of elt-5::mCherry expression (asterisks). i. rol-3(tm3908) animal arrested approximately at the L3 stage showing severe loss of elt-5::mCherry specification in the V lineage J. Quantification of the loss of seam cell specification in the H, V and T seam cell lineages in arrested rol-3(tm3908) animals. Scale bars, 25μm.

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).


The ortholog of the human proto-oncogene ROS1 is required for epithelial development in C. elegans.

Jones MR, Rose AM, Baillie DL - Genesis (2013)

Development of the seam syncytium is perturbed in animals carrying mutations in rol-3. a. Wild type L2 stage animal showing the characteristic ladder structure of the seam cells. b. rol-3(s1040ts) L2 animal raised a permissive temperature displaying a superficially wild type seam structure. c. WT adult seam syncytium is narrow and complete (arrow). d. Adult rol-3(s1040ts) animal displaying a disordered seam that is bifurcated (arrowheads). e. Arrested rol-3(s1040ts) animal. Two seam cells have elongated correctly (arrowhead) while an adjacent SCM::GFP expressing seam cell has ectopically fused with the hypodermis (arrow). A seam cell that has lost SCM::GFP expression and not elongated can be seen (asterisk). Several seam cells in the anterior of the animal have lost SCM::GFP expression and fused with the hypodermis (left image). f. Arrested rol-3(s126) animal showing a reduced number of AJM-1::GFP positive seam cells that have not elongated, note: several seam cells are not in the focal plane in this image (arrowheads). g. WT L3 animal expressing seam specific elt-5::mCherry. h. Arrested rol-3(s1040ts) animal with an L3 equivalent number of divided elt-5::mCherry positive cells. Note that the animal is much smaller than wildtype. Several cells of the V lineage have lost of elt-5::mCherry expression (asterisks). i. rol-3(tm3908) animal arrested approximately at the L3 stage showing severe loss of elt-5::mCherry specification in the V lineage J. Quantification of the loss of seam cell specification in the H, V and T seam cell lineages in arrested rol-3(tm3908) animals. Scale bars, 25μm.
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fig04: Development of the seam syncytium is perturbed in animals carrying mutations in rol-3. a. Wild type L2 stage animal showing the characteristic ladder structure of the seam cells. b. rol-3(s1040ts) L2 animal raised a permissive temperature displaying a superficially wild type seam structure. c. WT adult seam syncytium is narrow and complete (arrow). d. Adult rol-3(s1040ts) animal displaying a disordered seam that is bifurcated (arrowheads). e. Arrested rol-3(s1040ts) animal. Two seam cells have elongated correctly (arrowhead) while an adjacent SCM::GFP expressing seam cell has ectopically fused with the hypodermis (arrow). A seam cell that has lost SCM::GFP expression and not elongated can be seen (asterisk). Several seam cells in the anterior of the animal have lost SCM::GFP expression and fused with the hypodermis (left image). f. Arrested rol-3(s126) animal showing a reduced number of AJM-1::GFP positive seam cells that have not elongated, note: several seam cells are not in the focal plane in this image (arrowheads). g. WT L3 animal expressing seam specific elt-5::mCherry. h. Arrested rol-3(s1040ts) animal with an L3 equivalent number of divided elt-5::mCherry positive cells. Note that the animal is much smaller than wildtype. Several cells of the V lineage have lost of elt-5::mCherry expression (asterisks). i. rol-3(tm3908) animal arrested approximately at the L3 stage showing severe loss of elt-5::mCherry specification in the V lineage J. Quantification of the loss of seam cell specification in the H, V and T seam cell lineages in arrested rol-3(tm3908) animals. Scale bars, 25μm.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4. jonesmr@mail.ubc.ca

Show MeSH
Related in: MedlinePlus