Alternative temporal control systems for hypodermal cell differentiation in Caenorhabditis elegans


IN certain multicellular organisms, genetic regulatory systems that specify the timing of cell division, differentiation and morpho-genesis1–3 must accommodate environmental and physiological contingencies that perturb or arrest development. For example, Caenorhabditis elegans can either develop continuously through four larval stages (L1–L4) or arrest indefinitely as a 'dauer larva' at the second larval (L2) moult, and later resume L3 and L4 development4–7. At the larva-to-adult (L4) moult of both con-tinuous and 'post-dauer' development, hypodermal cells switch (the 'L/A switch') from a proliferating state to the terminally differentiated state. Four temporal regulators, lin-4, lin-14, lin-28 and lin-29, have been identified in C. elegans by mutations that cause precocious or retarded expression of stage-specific post-embryonic development events, including the L/A switch (refs 3, 8, 9; Fig. la). These genes have been organized into a genetic pathway that controls the timing of the L/A switch during continuous development10: lin-29 activates the switch and the other heterochronic genes regulate it indirectly by regulating lin-29. We have now examined how the proper timing of this event is specified in alternative developmental pathways. In continuously developing lin-4, lin-14 and lin-28 mutants the L/A switch occurs at abnor-mally early or late moults3,8, but during post-dauer development of the same mutants the L/A switch occurs normally. Thus hypodermal cell differentiation is regulated by separate temporal control systems, depending on the developmental history.


  1. 1

    Alberch, P., Gould, S. J., Oster, G. F. & Wake, D. B. Paleobiology 5, 296–317 (1979).

    Article  Google Scholar 

  2. 2

    Gould, S. J. Ontogeny and Phylogeny (Harvard University Press, Cambridge, Massachusetts, 1977).

    Google Scholar 

  3. 3

    Ambros, V. & Horvitz, H. R. Science 226, 409–416 (1984).

    CAS  Article  ADS  Google Scholar 

  4. 4

    Cassada, R. C. & Russell, R. L. Devl Biol. 46, 326–342 (1975).

    CAS  Article  Google Scholar 

  5. 5

    Evans, A. A. F. & Perry, R. M. in The Organization of Nematodes (ed. Croll, N. A.) (Academic, New YorK, 1976).

    Google Scholar 

  6. 6

    Golden, J. M. & Riddle, D. L. Science 218, 578–580 (1987).

    Article  ADS  Google Scholar 

  7. 7

    Riddle, D. L. in The Nematode Caenorhabditis elegans (eds Wood, W. B. and the community of C. elegans researchers) (Cold Spring Harbor Laboratory, New York, 1988).

    Google Scholar 

  8. 8

    Chalfie, M., Horvitz, R. H. & Sulston, J. E. Cell 24, 59–69 (1981).

    CAS  Article  Google Scholar 

  9. 9

    Ambros, V. & Horvitz, H. R. Genes Dev. 1, 398–414 (1987).

    CAS  Article  Google Scholar 

  10. 10

    Ambros, V. Cell 57, 49–57 (1989).

    CAS  Article  Google Scholar 

  11. 11

    Riddle, D. L., Swanson, M. M. & Alberts, P. S. Nature 290, 668–671 (1981).

    CAS  Article  ADS  Google Scholar 

  12. 12

    Liu, Z. & Ambros, V. Genes. Dev. 3, 2039–2049 (1989).

    CAS  Article  Google Scholar 

  13. 13

    Cox, G. N., Fields, C., Kramer, J. M., Rosenzweig, B. & Hirsh, D. Gene 76, 331–344 (1989).

    CAS  Article  Google Scholar 

  14. 14

    Cox, G. N. & Hirsh, D. Molec. cell. Biol. 5, 363–372 (1985).

    CAS  Article  Google Scholar 

  15. 15

    Ferguson, E. & Horvitz, H. R. Genetics 110, 17–72 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Cox, G. N., Laufer, J. S. Kusch, M. & Edgar, R. Genetics 95, 317–339 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Ruvkun, G. & Guisto, J. Nature 338, 313–319 (1989).

    CAS  Article  ADS  Google Scholar 

  18. 18

    Sulston, J. E. & Horvitz, R. H. Devl Biol. 56, 110–156 (1977).

    CAS  Article  Google Scholar 

  19. 19

    Kramer, J. M., French, R. P., Park, E. & Johnson, J. J. Molec. cell. Biol. 10 (1990).

  20. 20

    Fire, A., Harrison, S. & Dixon, D. Gene 93, 189–198 (1990).

    CAS  Article  Google Scholar 

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Liu, Z., Ambros, V. Alternative temporal control systems for hypodermal cell differentiation in Caenorhabditis elegans. Nature 350, 162–165 (1991).

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