Advertisement
JOURNAL ARTICLES
The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans
L.A. Wrischnik, C.J. Kenyon
Development 1997 124: 2875-2888;

Summary

In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.

REFERENCES

    1. Altschul S. F.,
    2. Gish W.,
    3. Miller W.,
    4. Myers E. W.,
    5. Lipman D. J.
    (1990) Basic local alignment search tool. J. Mol. Biol 215, 403–410
    OpenUrlCrossRefPubMedWeb of Science
    1. Ambros V.,
    2. Moss E. G.
    (1994) Heterochronic genes and the temporal control of C. elegans development.Trends Genet 10, 123–127
    OpenUrlCrossRefPubMedWeb of Science
    1. Austin J.,
    2. Kenyon C.
    (1994) Cell contact regulates neuroblast formation in the Caenorhabditis elegans lateral epidermis. Development 120, 313–323
    OpenUrlAbstract
    1. Bier E.,
    2. Vaessin H.,
    3. Younger-Shepherd S.,
    4. Jan L. Y.,
    5. Jan Y. N.
    (1992) deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. Genes Dev 6, 2137–51
    OpenUrlAbstract/FREE Full Text
    1. Brenner S.
    (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71–94
    OpenUrlAbstract/FREE Full Text
    1. Brown N. L.,
    2. Sattler C. A.,
    3. Markey D. R.,
    4. Carroll S. B.
    (1991) hairy gene function in the Drosophila eye: normal expression is dispensable but ectopic expression alters cell fates. Development 113, 1245–1256
    OpenUrlAbstract
    1. Brown N. L.,
    2. Sattler C. A.,
    3. Paddock S. W.,
    4. Carroll S. B.
    (1995) Hairy and emc negatively regulate morphogenetic furrow progression in the Drosophila eye. Cell 80, 879–87
    OpenUrlCrossRefPubMedWeb of Science
    1. Carroll S. B.,
    2. Scott M. P.
    (1986) Zygotically active genes that affect the spatial expression of the fushi tarazu segmentation gene during early Drosophila embryogenesis. Cell 45, 113–126
    OpenUrlCrossRefPubMedWeb of Science
    1. Carroll S. B.,
    2. Laughon A.,
    3. Thalley B. S.
    (1988) Expression, function, and regulation of the hairy segmentation protein in the Drosophila embryo. Genes Dev 2, 883–890
    OpenUrlAbstract/FREE Full Text
    1. Chisholm A.
    (1991) Control of cell fate in the tail region of C. elegans by the gene egl-5. Development 111, 921–932
    OpenUrlAbstract/FREE Full Text
    1. Chow K. L.,
    2. Emmons S. W.
    (1994) HOM-C/Hox genes and four interacting loci determine the morphogenetic properties of single cells in the nematode male tail. Development 120, 2579–2592
    OpenUrlAbstract/FREE Full Text
    1. Church G. M.,
    2. Gilbert W.
    (1984) Genomic sequencing. Proc. Natl. Acad. Sci. USA 81, 1991–1995
    OpenUrlAbstract/FREE Full Text
    1. Clark S. G.,
    2. Chisholm A. D.,
    3. Horvitz H. R.
    (1993) Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39. Cell 74, 43–54
    OpenUrlCrossRefPubMedWeb of Science
    1. Costa M.,
    2. Weir M.,
    3. Coulson A.,
    4. Sulston J.,
    5. Kenyon C.
    (1988) Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox. Cell 55, 747–756
    OpenUrlCrossRefPubMedWeb of Science
    1. Coulson A.,
    2. Waterston R.,
    3. Kiff J.,
    4. Sulston J.,
    5. Kohara Y.
    (1988) Genome linking with yeast artificial chromosomes. Nature 335, 184–186
    OpenUrlCrossRefPubMedWeb of Science
    1. Dawson S. R.,
    2. Turner D. L.,
    3. Weintraub H.,
    4. Parkhurst S. M.
    (1995) Specificity for the hairy/Enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression. Mol. Cell. Biol 15, 6923–6931
    OpenUrlAbstract/FREE Full Text
    1. Delidakis C.,
    2. Artavanis-Tsakonas S.
    (1992) The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins. Proc. Natl. Acad. Sci. USA 89, 8731–8735
    OpenUrlAbstract/FREE Full Text
    1. Feder J. N.,
    2. Jan L. Y.,
    3. Jan Y. N.
    (1993) A rat gene with sequence homology to the Drosophila gene hairy is rapidly induced by growth factors known to influence neuronal differentiation. Mol. Cell Biol 13, 105–113
    OpenUrlAbstract/FREE Full Text
    1. Frohman M. A.
    (1994) On beyond classic RACE (rapid amplification of cDNA ends). PCR Methods Applic 4, 40–.
    OpenUrl
    1. Ghysen A.,
    2. Dambly C. C.,
    3. Jan L. Y.,
    4. Jan Y. N.
    (1993) Cell interactions and gene interactions in peripheral neurogenesis. Genes Dev 7, 723–733
    OpenUrlFREE Full Text
    1. Gish W.,
    2. States D. J.
    (1993) Identification of protein coding regions by database similarity search. Nat. Genet 3, 266–272
    OpenUrlCrossRefPubMedWeb of Science
    1. Horvitz H. R.,
    2. Sternberg P. W.,
    3. Greenwald I. S.,
    4. Fixsen W.,
    5. Ellis H. M.
    (1983) Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans. Cold Spring Harb. Symp. Quant. Biol 48, 453–63
    1. Howard K.,
    2. Ingham P.
    (1986) Regulatory interactions between the segmentation genes fushi tarazu, hairy, and engrailed in the Drosophila blastoderm. Cell 44, 949–57
    OpenUrlCrossRefPubMedWeb of Science
    1. Howard K.,
    2. Struhl G.
    (1990) Decoding positional information: regulation of the pair-rule gene hairy. Development 110, 1223–1231
    OpenUrlAbstract/FREE Full Text
    1. Hunter C. P.,
    2. Kenyon C.
    (1995) Specification of anteroposterior cell fates in Caenorhabditis elegans by Drosophila Hox proteins. Nature 377, 229–232
    OpenUrlCrossRefPubMedWeb of Science
    1. Ingham P. W.,
    2. Pinchin S. M.,
    3. Howard K. R.,
    4. Ish-Horowicz D.
    (1985) Genetic analysis of the hairy locus in Drosophila melanogaster. Genetics 111, 463–486
    OpenUrlAbstract/FREE Full Text
    1. Ish-Horowicz D.,
    2. Pinchin S. M.
    (1987) Pattern abnormalities induced by ectopic expression of the Drosophila gene hairy are associated with repression of ftz transcription. Cell 51, 405–415
    OpenUrlCrossRefPubMedWeb of Science
    1. Ishibashi M.,
    2. Sasai Y.,
    3. Nakanishi S.,
    4. Kageyama R.
    (1993) Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split. Eur. J. Biochem 215, 645–652
    OpenUrlPubMedWeb of Science
    1. Ishibashi M.,
    2. Ang S. L.,
    3. Shiota K.,
    4. Nakanishi S.,
    5. Kageyama R.,
    6. Guillemot F.
    (1995) Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev 9, 3136–3148
    OpenUrlAbstract/FREE Full Text
    1. Jack T.,
    2. McGinnis W.
    (1990) Establishment of the Deformed expression stripe requires the combinatorial action of coordinate, gap and pair-rule proteins. EMBO J 9, 1187–1198
    OpenUrlPubMedWeb of Science
    1. Kenyon C.
    (1986) A gene involved in the development of the posterior body region of C. elegans. Cell 46, 477–87
    OpenUrlCrossRefPubMedWeb of Science
    1. Kimmel C. B.
    (1996) Was Urbilateria segmented?. Trends in Genetics 12, 329–331
    OpenUrlPubMedWeb of Science
    1. Klambt C.,
    2. Knust E.,
    3. Tietze K.,
    4. Campos-Ortega J. A.
    (1987) Closely related transcripts encoded by the neurogenic gene complex Enhancer of split of Drosophila melanogaster. EMBO J 6, 4113–4123
    OpenUrlPubMedWeb of Science
    1. Knust E.,
    2. Schrons H.,
    3. Grawe F.,
    4. Campos-Ortega J. A.
    (1992) Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins. Genetics 132, 505–518
    OpenUrlAbstract/FREE Full Text
    1. Krause M.,
    2. Hirsh D.
    (1987) A trans-spliced leader sequence on actin mRNA in C. elegans. Cell 49, 753–761
    OpenUrlCrossRefPubMedWeb of Science
    1. Lewis J. A.,
    2. Fleming J. T.
    (1995) Basic culture methods. Meth. Cell Biol 48, 4–29
    OpenUrl
    1. Macias A.,
    2. Pelaz S.,
    3. Morata G.
    (1994) Genetic factors controlling the expression of the abdominal-A gene of Drosophila within its domain. Mech. Dev 46, 15–25
    OpenUrlCrossRefPubMed
    1. Mello C. C.,
    2. Kramer J. M.,
    3. Stinchcomb D.,
    4. Ambros V.
    (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10, 3959–3970
    OpenUrlPubMedWeb of Science
    1. Muller M.,
    2. Weizsacker E.,
    3. Campos-Ortega J. A.
    (1996) Expression domains of a zebrafish homologue of the Drosophila pair-rule gene hairy correspond to primordia of alternating somites. Development 122, 2071–2078
    OpenUrlAbstract
    1. Ohsako S.,
    2. Hyer J.,
    3. Panganiban G.,
    4. Oliver I.,
    5. Caudy M.
    (1994) hairy function as a DNA-binding helix-loop-helix repressor of Drosophila sensory organ formation. Genes Dev 8, 2743–2755
    OpenUrlAbstract/FREE Full Text
    1. Orenic T. V.,
    2. Held L. I., Jr.,
    3. Paddock S. W.,
    4. Carroll S. B.
    (1993) The spatial organization of epidermal structures: hairy establishes the geometrical pattern of Drosophila leg bristles by delimiting the domains of achaete expression. Development 118, 9–20
    OpenUrlAbstract
    1. Pankratz M. J.,
    2. Seifert E.,
    3. Gerwin N.,
    4. Billi B.,
    5. Nauber U.,
    6. Jackle H.
    (1990) Gradients of Kruppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo. Cell 61, 309–317
    OpenUrlCrossRefPubMedWeb of Science
    1. Paroush Z.,
    2. Finley R. L., Jr.,
    3. Kidd T.,
    4. Wainwright S. M.,
    5. Ingham P. W.,
    6. Brent R.,
    7. Ish-Horowicz D.
    (1994) Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy -related bHLH proteins. Cell 79, 805–815
    OpenUrlCrossRefPubMedWeb of Science
    1. Riddihough G.,
    2. Ish-Horowicz D.
    (1991) Individual stripe regulatory elements in the Drosophilahairy promoter respond to maternal, gap, and pair-rule genes. Genes Dev 5, 840–854
    OpenUrlAbstract/FREE Full Text
    1. Ruvkun G.,
    2. Ambros V.,
    3. Coulson A.,
    4. Waterston R.,
    5. Sulston J.,
    6. Horvitz H. R.
    (1989) Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14. Genetics 121, 501–516
    OpenUrlAbstract/FREE Full Text
    1. Salser S. J.,
    2. Kenyon C. J.
    (1996) A C. elegans Hox gene switches on, off, on and off again to regulate proliferation, differentiation, and morphogenesis. Development 122, 1651–1661
    OpenUrlAbstract
    1. Salser S. J.,
    2. Loer C. M.,
    3. Kenyon C. J.
    (1993) Multiple HOM-C gene interactions specify cell fates in the nematode central nervous system. Genes Dev 7, 1714–1724
    OpenUrlAbstract/FREE Full Text
    1. Sasai Y.,
    2. Kageyama R.,
    3. Tagawa Y.,
    4. Shigemoto R.,
    5. Nakanishi S.
    (1992) Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev 6, 2620–2634
    OpenUrlAbstract/FREE Full Text
    1. Schaller D.,
    2. Wittmann C.,
    3. Spicher A.,
    4. Muller F.,
    5. Tobler H.
    (1990) Cloning and analysis of three new homeobox genes from the nematode C. elegans. Nucl. Acids Res 18, 2033–2036
    OpenUrlAbstract/FREE Full Text
    1. Shackleford G. M.,
    2. Shivakumar S.,
    3. Shiue L.,
    4. Mason J.,
    5. Kenyon C.,
    6. Varmus H. E.
    (1993) Two wnt genes in Caenorhabditis elegans. Oncogene 8, 1857–1864
    OpenUrlPubMed
    1. Skeath J. B.,
    2. Carroll S. B.
    (1991) Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. Genes Dev 5, 984–995
    OpenUrlAbstract/FREE Full Text
    1. Sommer R. J.,
    2. Tautz D.
    (1993) Involvement of an orthologue of the Drosophila pair-rule gene hairy in segment formation of the short germ-band embryo of Tribolium (Coleoptera). Nature 361, 448–450
    OpenUrlCrossRefPubMed
    1. Sulston J.,
    2. Albertson D.,
    3. Thomson J.
    (1980) The C elegans male: Postembryonic development of nongonadal structures. Dev. Biol 78, 542–576
    OpenUrlCrossRefPubMedWeb of Science
    1. Sulston J.,
    2. Horvitz H.
    (1977) Post-embryonic cell lineages of the nematode, C elegans. Dev. Biol 56, 110–156
    OpenUrlCrossRefPubMedWeb of Science
    1. Takebayashi K.,
    2. Sasai Y.,
    3. Sakai Y.,
    4. Watanabe T.,
    5. Nakanishi S.,
    6. Kageyama R.
    (1994) Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements. J. Biol. Chem 269, 5150–5156
    OpenUrlAbstract/FREE Full Text
    1. Van Doren M.,
    2. Bailey A. M.,
    3. Esnayra J.,
    4. Ede K.,
    5. Posakony J. W.
    (1994) Negative regulation of proneural gene activtiy: hairy is a direct transcriptional repressor of achaete. Genes & Dev 8, 2729–2742
    OpenUrlAbstract/FREE Full Text
    1. Wainwright S. M.,
    2. Ish-Horowicz D.
    (1992) Point mutations in the Drosophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. Mol. Cell. Biol 12, 2475–2483
    OpenUrlAbstract/FREE Full Text
    1. Wang B. B.,
    2. Muller-Immergluck M. M.,
    3. Austin J.,
    4. Robinson N. T.,
    5. Chisholm A.,
    6. Kenyon C.
    (1993) A homeotic gene cluster patterns the anteroposterior body axis of C. elegans. Cell 74, 29–42
    OpenUrlCrossRefPubMedWeb of Science
    1. Waring D. A.,
    2. Kenyon C.
    (1991) Regulation of cellular responsiveness to inductive signals in the developing C. elegans nervous system. Nature 350, 712–715
    OpenUrlCrossRefPubMed
    1. Waring D. A.,
    2. Wrischnik L.,
    3. Kenyon C.
    (1992) Cell signals allow the expression of a pre-existent neural pattern in C. elegans. Development 116, 457–466
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans
L.A. Wrischnik, C.J. Kenyon
Development 1997 124: 2875-2888;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.