From egg through adult, C. elegans has six life stages including an option for dauer formation and diapause at larval stage L3 in adverse environments. Somatic cells throughout the organism make consistent choices and advance in unison, suggesting a mechanism of coordinate regulation at these stage transitions. Earlier studies showed that daf-12, which encodes a nuclear receptor (W. Yeh, 1991, Doctoral Thesis. University of Missouri-Columbia), regulates dauer formation; epistasis experiments placed daf-12 near the end of the dauer signaling pathway. Here we describe novel daf-12 alleles that reveal a general role in advancing L3 stage programs. In these mutants, somatic cells repeat L2-specific cellular programs of division and migration at the L3 stage; epistasis experiments place daf-12 between lin-14 and lin-28 within the heterochronic pathway. We propose daf-12 and other heterochronic genes provide cellular memories of chronological stage for selecting stage-appropriate developmental programs. Endocrine factors could coordinate these stage transitions and specify developmental alternatives.

Ambros
V.
(
1989
)
A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans.
Cell
57
,
49
57
Ambros
V.
,
Horvitz
H. R.
(
1984
)
Heterochronic mutants of the nematode C. elegans.
Science
226
,
409
416
Ambros
V.
,
Horvitz
H. R.
(
1987
)
The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific post-embryonic developmental events.
Genes Dev
1
,
398
414
Arasu
P.
,
Wightman
B.
,
Ruvkun
G.
(
1991
)
Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes lin-4 and lin-28.
Genes Dev
5
,
1825
1833
Austin
J.
,
Kimble
J.
(
1987
)
glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans.
Cell
51
,
589
599
Bettinger
J. C.
,
Lee
K.
,
Rougvie
A. E.
(
1996
)
Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development.
Development
122
,
2517
2527
Cassada
R. C.
,
Russell
R. L.
(
1975
)
The Dauer-Larva: A Post-Embryonic Developmental Variant of the Nematode C. elegans.
Dev. Biol
46
,
326
342
Chalfie
M.
,
Horvitz
H. R.
,
Sulston
J. E.
(
1981
)
Mutations that lead to reiterations in the cell lineages of C. elegans.
Cell
24
,
59
69
Dorman
J. B.
,
Albinder
B.
,
Shroyer
T.
,
Kenyon
C.
(
1995
)
The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans.
Genetics
141
,
1399
1406
Euling
S.
,
Ambros
V.
(
1996
)
Reversal of cell fate determination in Caenorhabditis elegans vulval development.
Development
122
,
2507
2515
Golden
J. W.
,
Riddle
D. L.
(
1984
)
The C. elegans dauer larva, developmental effects of pheromone food and temperature.
Dev. Biol
102
,
368
378
Gottlieb
S.
,
Ruvkun
G.
(
1994
)
daf-2, daf-16 and daf-23: genetically interacting genes controlling dauer formation in Caenorhabditis elegans.
Genetics
137
,
107
120
Hedgecock
E. M.
,
Culotti
J. G.
,
Hall
D. H.
,
Stern
B. D.
(
1987
)
Genetics of cell and axon migrations in Caenorhabditis elegans.
Development
100
,
365
382
Hedgecock
E. M.
,
White
J. G.
(
1985
)
Polyploid tissues in the nematode C. elegans.
Dev. Biol
107
,
128
133
Hodgkin
J.
,
Horvitz
H. R.
,
Brenner
S.
(
1979
)
Nondisjunction mutants of the nematode C aenorhabditis elegans.
Genetics
91
,
67
94
Johnson
T. E.
,
Mitchell
D. H.
,
Kline
S.
,
Kemal
R.
,
Foy
J.
(
1984
)
Arresting development arrests aging in the nematode C. elegans.
Mech. Ageing Dev
28
,
23
40
Johnstone
I. L.
,
Barry
D. J.
(
1996
)
Temporal reiteration of a precise gene expression pattern during nematode development.
EMBO J
15
,
3633
39
Kenyon
C.
,
Chang
J.
,
Gensch
E.
,
Rudner
A.
,
Tabtlang
R.
(
1993
)
A C. elegans mutant that lives twice as long as wild type.
Nature
366
,
461
464
Kimble
J.
,
Hirsh
D.
(
1979
)
The post-embryonic cell lineages of the hermaphrodite and male gonads in C. elegans.
Dev. Biol
70
,
396
417
Kimble
J.
(
1981
)
Alterations in cell lineage following laser ablation of cells in the somatic gonad of Caenorhabditis elegans.
Dev. Biol
87
,
286
300
Kimble
J.
,
White
J. G.
(
1981
)
On the control of germline cell development in C. elegans.
Dev. Biol
81
,
208
221
Kimura
K. D.
,
Tissenbaum
H. A.
,
Liu
Y.
,
Ruvkun
G.
(
1997
)
daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.
Science
277
,
942
946
Larsen
P. L.
,
Albert
P. S.
,
Riddle
D. L.
(
1995
)
Genes that regulate both development and longevity in C. elegans.
Genetics
139
,
1553
1566
Lee
R. C.
,
Feinbaum
R. L.
,
Ambros
V.
(
1993
)
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
Cell
5
,
843
854
Lin
K.
,
Dorman
J. B.
,
Rodan
A.
,
Kenyon
C.
(
1997
)
daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.
Science
278
,
1319
1322
Liu
Z.
,
Ambros
V.
(
1989
)
, Heterochronic genes control the stage-specific initiation and expression of the dauer larval developmental program in Caenorhabditis elegans.
Genes Dev
3
,
2039
2049
Liu
Z.
,
Ambros
V.
(
1991
)
Alternative temporal control systems for hypodermal cell differentiation in C elegans.
Nature
350
,
162
165
Morris
J. Z.
,
Tissenbaum
H. A.
,
Ruvkun
G.
(
1996
)
A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans.
Nature
382
,
536
539
Moss
E. G.
,
Lee
R. C.
,
Ambros
V.
(
1997
)
The Cold Shock Domain Protein LIN-28 Controls Developmental Timing in C. elegans and Is Regulated by the lin-4 RNA.
Cell
88
,
637
646
Newman
A. P.
,
White
J. G.
,
Sternberg
P. W.
(
1996
)
Morphogenesis of the C. elegans hermaphrodite uterus.
Development
122
,
3617
3626
Ogg
S.
,
Paradis
S.
,
Gottlieb
S.
,
Patterson
G. I.
,
Lee
L.
,
Tissenbaum
H. A.
,
Ruvkun
G.
(
1997
)
The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.
Nature
389
,
994
999
Ren
P.
,
Lim
C. S.
,
Johnsen
R.
,
Albert
P. S.
,
Pilgrim
D.
,
Riddle
D. L.
(
1996
)
Control of C. elegans Larval Development by Neuronal Expression of a TGF-Homolog.
Science
274
,
1389
91
Riddle
D. L.
,
Swanson
M. M.
,
Albert
P. S.
(
1981
)
Interacting genes in nematode dauer larva formation.
Nature
290
,
668
671
Rougvie
A. E.
,
Ambros
V.
(
1995
)
The heterochronic gene lin-29 encodes a zinc finger protein that controls a terminal differentiation event in Caenorhabditis elegans.
Development
121
,
2491
2500
Ruvkun
G.
,
Giusto
J.
(
1989
)
The C. elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch.
Nature
338
,
313
319
Sulston
J. E.
,
Horvitz
H. R.
(
1977
)
Post-embryonic cell lineages of the nematode C. elegans.
Dev. Biol
56
,
110
156
Sulston
J. E.
,
Albertson
D. G.
,
Thomson
J. N.
(
1980
)
The C. elegans male: post-embryonic development of non-gonadal structures.
Dev. Biol
78
,
542
576
Sulston
J. E.
,
Schierenberg
E.
,
White
J. G.
,
Thomson
J. N.
(
1983
)
The embryonic cell lineage of the nematode C. elegans.
Dev. Biol
100
,
64
119
Swanson
M. M.
,
Riddle
D. L.
(
1981
)
Critical periods in the development of the Caenorhabditis elegans dauer larva.
Dev. Biol
84
,
27
40
Thomas
J. H.
,
Birnby
D. A.
,
Vowels
J. J.
(
1993
)
Evidence for parallel processing of sensory information controlling dauer formation in C. elegans.
Genetics
134
,
1105
1117
Thummel
C. S.
(
1995
)
From embryogenesis to metamorphosis: the regulation and function of Drosophila nuclear receptor superfamily members.
Cell
83
,
871
877
Vowels
J. J.
,
Thomas
J. H.
(
1992
)
Genetic analysis of chemosensory control of dauer formation in C. elegans.
Genetics
130
,
105
123
Wightman
B.
,
Ha
I.
,
Ruvkun
G.
(
1993
)
Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
Cell
75
,
855
862
This content is only available via PDF.