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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  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 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing