Abstract
To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ~67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.
Full Text
The Full Text of this article is available as a PDF (7.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahnn J., Fire A. A screen for genetic loci required for body-wall muscle development during embryogenesis in Caenorhabditis elegans. Genetics. 1994 Jun;137(2):483–498. doi: 10.1093/genetics/137.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Albertson D. G., Sulston J. E., White J. G. Cell cycling and DNA replication in a mutant blocked in cell division in the nematode Caenorhabditis elegans. Dev Biol. 1978 Mar;63(1):165–178. doi: 10.1016/0012-1606(78)90122-7. [DOI] [PubMed] [Google Scholar]
- Ambros V., Horvitz H. R. The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Genes Dev. 1987 Jun;1(4):398–414. doi: 10.1101/gad.1.4.398. [DOI] [PubMed] [Google Scholar]
- Anderson P., Brenner S. A selection for myosin heavy chain mutants in the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4470–4474. doi: 10.1073/pnas.81.14.4470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barton M. K., Kimble J. fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans. Genetics. 1990 May;125(1):29–39. doi: 10.1093/genetics/125.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blau H. M. How fixed is the differentiated state? Lessons from heterokaryons. Trends Genet. 1989 Aug;5(8):268–272. doi: 10.1016/0168-9525(89)90100-5. [DOI] [PubMed] [Google Scholar]
- Bowerman B., Eaton B. A., Priess J. R. skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell. 1992 Mar 20;68(6):1061–1075. doi: 10.1016/0092-8674(92)90078-q. [DOI] [PubMed] [Google Scholar]
- Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capowski E. E., Martin P., Garvin C., Strome S. Identification of grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditis elegans. Genetics. 1991 Dec;129(4):1061–1072. doi: 10.1093/genetics/129.4.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Charest D. L., Clark D. V., Green M. E., Baillie D. L. Genetic and fine structure analysis of unc-26(IV) and adjacent regions in Caenorhabditis elegans. Mol Gen Genet. 1990 May;221(3):459–465. doi: 10.1007/BF00259412. [DOI] [PubMed] [Google Scholar]
- Chen L., Krause M., Draper B., Weintraub H., Fire A. Body-wall muscle formation in Caenorhabditis elegans embryos that lack the MyoD homolog hlh-1. Science. 1992 Apr 10;256(5054):240–243. doi: 10.1126/science.1314423. [DOI] [PubMed] [Google Scholar]
- Chisholm A. Control of cell fate in the tail region of C. elegans by the gene egl-5. Development. 1991 Apr;111(4):921–932. doi: 10.1242/dev.111.4.921. [DOI] [PubMed] [Google Scholar]
- Clark D. V., Johnsen R. C., McKim K. S., Baillie D. L. Analysis of lethal mutations induced in a mutator strain that activates transposable elements in Caenorhabditis elegans. Genome. 1990 Feb;33(1):109–114. doi: 10.1139/g90-017. [DOI] [PubMed] [Google Scholar]
- Clark D. V., Rogalski T. M., Donati L. M., Baillie D. L. The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations. Genetics. 1988 Jun;119(2):345–353. doi: 10.1093/genetics/119.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark S. G., Chisholm A. D., Horvitz H. R. Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39. Cell. 1993 Jul 16;74(1):43–55. doi: 10.1016/0092-8674(93)90293-y. [DOI] [PubMed] [Google Scholar]
- Clark S. G., Lu X., Horvitz H. R. The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. Genetics. 1994 Aug;137(4):987–997. doi: 10.1093/genetics/137.4.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeLong L., Plenefisch J. D., Klein R. D., Meyer B. J. Feedback control of sex determination by dosage compensation revealed through Caenorhabditis elegans sdc-3 mutations. Genetics. 1993 Apr;133(4):875–896. doi: 10.1093/genetics/133.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eeckman F. H., Durbin R. ACeDB and macace. Methods Cell Biol. 1995;48:583–605. [PubMed] [Google Scholar]
- Ellis R. E., Horvitz H. R. Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development. 1991 Jun;112(2):591–603. doi: 10.1242/dev.112.2.591. [DOI] [PubMed] [Google Scholar]
- Gendreau S. B., Moskowitz I. P., Terns R. M., Rothman J. H. The potential to differentiate epidermis is unequally distributed in the AB lineage during early embryonic development in C. elegans. Dev Biol. 1994 Dec;166(2):770–781. doi: 10.1006/dbio.1994.1355. [DOI] [PubMed] [Google Scholar]
- Gilchrist E. J., Moerman D. G. Mutations in the sup-38 gene of Caenorhabditis elegans suppress muscle-attachment defects in unc-52 mutants. Genetics. 1992 Oct;132(2):431–442. doi: 10.1093/genetics/132.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- González-Gaitán M., Rothe M., Wimmer E. A., Taubert H., Jäckle H. Redundant functions of the genes knirps and knirps-related for the establishment of anterior Drosophila head structures. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8567–8571. doi: 10.1073/pnas.91.18.8567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenwald I. S., Horvitz H. R. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. Genetics. 1980 Sep;96(1):147–164. doi: 10.1093/genetics/96.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grether M. E., Abrams J. M., Agapite J., White K., Steller H. The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev. 1995 Jul 15;9(14):1694–1708. doi: 10.1101/gad.9.14.1694. [DOI] [PubMed] [Google Scholar]
- Hecht R. M., Berg-Zabelshansky M., Rao P. N., Davis F. M. Conditional absence of mitosis-specific antigens in a temperature-sensitive embryonic-arrest mutant of Caenorhabditis elegans. J Cell Sci. 1987 Mar;87(Pt 2):305–314. doi: 10.1242/jcs.87.2.305. [DOI] [PubMed] [Google Scholar]
- Hengartner M. O., Ellis R. E., Horvitz H. R. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature. 1992 Apr 9;356(6369):494–499. doi: 10.1038/356494a0. [DOI] [PubMed] [Google Scholar]
- Hodgkin J. A., Brenner S. Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. Genetics. 1977 Jun;86(2 Pt 1):275–287. [PMC free article] [PubMed] [Google Scholar]
- Hodgkin J. Primary sex determination in the nematode C. elegans. Development. 1987;101 (Suppl):5–16. doi: 10.1242/dev.101.Supplement.5. [DOI] [PubMed] [Google Scholar]
- Hope I. A. 'Promoter trapping' in Caenorhabditis elegans. Development. 1991 Oct;113(2):399–408. doi: 10.1242/dev.113.2.399. [DOI] [PubMed] [Google Scholar]
- Howell A. M., Rose A. M. Essential genes in the hDf6 region of chromosome I in Caenorhabditis elegans. Genetics. 1990 Nov;126(3):583–592. doi: 10.1093/genetics/126.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang L. S., Tzou P., Sternberg P. W. The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. Mol Biol Cell. 1994 Apr;5(4):395–411. doi: 10.1091/mbc.5.4.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hutter H., Schnabel R. Establishment of left-right asymmetry in the Caenorhabditis elegans embryo: a multistep process involving a series of inductive events. Development. 1995 Oct;121(10):3417–3424. doi: 10.1242/dev.121.10.3417. [DOI] [PubMed] [Google Scholar]
- Hutter H., Schnabel R. glp-1 and inductions establishing embryonic axes in C. elegans. Development. 1994 Jul;120(7):2051–2064. doi: 10.1242/dev.120.7.2051. [DOI] [PubMed] [Google Scholar]
- Ingham P. W. The molecular genetics of embryonic pattern formation in Drosophila. Nature. 1988 Sep 1;335(6185):25–34. doi: 10.1038/335025a0. [DOI] [PubMed] [Google Scholar]
- Labouesse M., Sookhareea S., Horvitz H. R. The Caenorhabditis elegans gene lin-26 is required to specify the fates of hypodermal cells and encodes a presumptive zinc-finger transcription factor. Development. 1994 Sep;120(9):2359–2368. doi: 10.1242/dev.120.9.2359. [DOI] [PubMed] [Google Scholar]
- Lambie E. J., Kimble J. Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development. 1991 May;112(1):231–240. doi: 10.1242/dev.112.1.231. [DOI] [PubMed] [Google Scholar]
- Link C. D., Silverman M. A., Breen M., Watt K. E., Dames S. A. Characterization of Caenorhabditis elegans lectin-binding mutants. Genetics. 1992 Aug;131(4):867–881. doi: 10.1093/genetics/131.4.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maine E. M., Kimble J. Suppressors of glp-1, a gene required for cell communication during development in Caenorhabditis elegans, define a set of interacting genes. Genetics. 1993 Dec;135(4):1011–1022. doi: 10.1093/genetics/135.4.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mains P. E., Kemphues K. J., Sprunger S. A., Sulston I. A., Wood W. B. Mutations affecting the meiotic and mitotic divisions of the early Caenorhabditis elegans embryo. Genetics. 1990 Nov;126(3):593–605. doi: 10.1093/genetics/126.3.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mango S. E., Lambie E. J., Kimble J. The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans. Development. 1994 Oct;120(10):3019–3031. doi: 10.1242/dev.120.10.3019. [DOI] [PubMed] [Google Scholar]
- Mango S. E., Thorpe C. J., Martin P. R., Chamberlain S. H., Bowerman B. Two maternal genes, apx-1 and pie-1, are required to distinguish the fates of equivalent blastomeres in the early Caenorhabditis elegans embryo. Development. 1994 Aug;120(8):2305–2315. doi: 10.1242/dev.120.8.2305. [DOI] [PubMed] [Google Scholar]
- McKim K. S., Peters K., Rose A. M. Two types of sites required for meiotic chromosome pairing in Caenorhabditis elegans. Genetics. 1993 Jul;134(3):749–768. doi: 10.1093/genetics/134.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKim K. S., Starr T., Rose A. M. Genetic and molecular analysis of the dpy-14 region in Caenorhabditis elegans. Mol Gen Genet. 1992 May;233(1-2):241–251. doi: 10.1007/BF00587585. [DOI] [PubMed] [Google Scholar]
- Mello C. C., Draper B. W., Priess J. R. The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo. Cell. 1994 Apr 8;77(1):95–106. doi: 10.1016/0092-8674(94)90238-0. [DOI] [PubMed] [Google Scholar]
- Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meneely P. M., Herman R. K. Lethals, steriles and deficiencies in a region of the X chromosome of Caenorhabditis elegans. Genetics. 1979 May;92(1):99–115. doi: 10.1093/genetics/92.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merrill P. T., Sweeton D., Wieschaus E. Requirements for autosomal gene activity during precellular stages of Drosophila melanogaster. Development. 1988 Nov;104(3):495–509. doi: 10.1242/dev.104.3.495. [DOI] [PubMed] [Google Scholar]
- Miller L. M., Plenefisch J. D., Casson L. P., Meyer B. J. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell. 1988 Oct 7;55(1):167–183. doi: 10.1016/0092-8674(88)90019-0. [DOI] [PubMed] [Google Scholar]
- Pilgrim D., McGregor A., Jäckle P., Johnson T., Hansen D. The C. elegans sex-determining gene fem-2 encodes a putative protein phosphatase. Mol Biol Cell. 1995 Sep;6(9):1159–1171. doi: 10.1091/mbc.6.9.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Podbilewicz B., White J. G. Cell fusions in the developing epithelial of C. elegans. Dev Biol. 1994 Feb;161(2):408–424. doi: 10.1006/dbio.1994.1041. [DOI] [PubMed] [Google Scholar]
- Priess J. R., Hirsh D. I. Caenorhabditis elegans morphogenesis: the role of the cytoskeleton in elongation of the embryo. Dev Biol. 1986 Sep;117(1):156–173. doi: 10.1016/0012-1606(86)90358-1. [DOI] [PubMed] [Google Scholar]
- Priess J. R., Schnabel H., Schnabel R. The glp-1 locus and cellular interactions in early C. elegans embryos. Cell. 1987 Nov 20;51(4):601–611. doi: 10.1016/0092-8674(87)90129-2. [DOI] [PubMed] [Google Scholar]
- Riddle D. L., Brenner S. Indirect suppression in Caenorhabditis elegans. Genetics. 1978 Jun;89(2):299–314. doi: 10.1093/genetics/89.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogalski T. M., Moerman D. G., Baillie D. L. Essential genes and deficiencies in the unc-22 IV region of Caenorhabditis elegans. Genetics. 1982 Dec;102(4):725–736. doi: 10.1093/genetics/102.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schrons H., Knust E., Campos-Ortega J. A. The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. Genetics. 1992 Oct;132(2):481–503. doi: 10.1093/genetics/132.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sigurdson D. C., Spanier G. J., Herman R. K. Caenorhabditis elegans deficiency mapping. Genetics. 1984 Oct;108(2):331–345. doi: 10.1093/genetics/108.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith A. V., King J. A., Orr-Weaver T. L. Identification of genomic regions required for DNA replication during Drosophila embryogenesis. Genetics. 1993 Nov;135(3):817–829. doi: 10.1093/genetics/135.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
