The E proteins of mammals, and the related Daughterless (DA) protein of Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription factors that play a role in many developmental processes. We report here the characterization of a related C. elegans protein, CeE/DA, which has a dynamic and restricted distribution during development. CeE/DA is present embryonically in neuronal precursors, some of which are marked by promoter activity of a newly described Achaete-scute-like gene hlh-3. In contrast, we have been unable to detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility shift analysis detects dimerization of CeE/DA with HLH-3 while efficient interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple roles for CeE/DA in C. elegans development and provide evidence that both common and alternative strategies have evolved for the use of related HLH proteins in controlling cell fates in different species.

REFERENCES

REFERENCES
Akazawa
C.
,
Ishibashi
M.
,
Shimizu
C.
,
Nakanishi
S.
,
Kageyama
R.
(
1995
)
A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system.
J. Biol. Chem
270
,
8730
8738
Albertson
D. G.
,
Thomson
J. N.
(
1975
)
The pharynx of Caenorhabditis elegans.
Phil. Trans. R. Soc. London
275
,
299
325
Ardizzi
J. P.
,
Epstein
H. F.
(
1987
)
Immunochemical localization of myosin heavy chain isoforms and paramyosin in developmentally and structurally diverse muscle cell types of the nematode Caenorhabditis elegans.
J. Cell Biol
105
,
2763
2770
Armand
P.
,
Knapp
A.
,
Hirsch
A.
,
Wieschaus
E.
,
Cole
M.
(
1994
)
A novel basic helix-loop-helix protein is expressed in the muscle attachment sites of the Drosophila epidermis.
Mol. Cell Biol
14
,
4145
4154
Bain
G.
,
Maandag
E. C. R.
,
Izon
D. J.
,
Amsen
D.
,
Kruisbeek
A. M.
,
Weintraub
B. C.
,
Krop
I.
,
Schlissel
M. S.
,
Feeney
A. J.
,
ban Roon
M.
,
van der Valk
M.
,
te Riele
H. P. J.
,
Berns
A.
,
Murre
C.
(
1994
)
E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements.
Cell
79
,
885
892
Barstead
R. J.
,
Waterston
R. H.
(
1989
)
The basal component of the nematode dense-body is vinculin.
J. Biol. Chem
264
,
10177
10185
Benezra
R.
(
1994
)
An intermolecular disulfide bond stabilizes E2A homodimers and is required for DNA binding at physiological temperatures.
Cell
79
,
1057
1067
Blumenthal
T.
(
1995
)
Trans- splicing and polycistronic transcription in Caenorabditis elegans.
Trends Genet
11
,
132
136
Burden
S. J.
(
1993
)
Synapse-specific gene expression.
Trends Genet
9
,
12
16
Cabrera
C. V.
,
Alonso
M.
(
1991
)
Transcriptional activiation by heterodimers of the achaete-scute and daughterless gene products of Drosophila.
EMBO J
10
,
2965
2973
Caudy
M.
,
Vassin
H.
,
Brand
M.
,
Tuma
R.
,
Jan
L. Y.
,
Jan
Y. N.
(
1988
)
daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex.
Cell
55
,
1061
1067
Caudy
M.
,
Grell
E. H.
,
Dambly-Chaudiere
C.
,
Ghysen
A.
,
Jan
L. Y.
,
Jan
Y. N.
(
1988
)
The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila.
Genes Dev
2
,
843
852
Chen
L.
,
Krause
M. W.
,
Draper
B.
,
Weintraub
H.
,
Fire
A.
(
1992
)
Body-wall muscle formation in Caenorhabditis elegans embryos that lack the MyoD homolog hlh-1.
Science
256
,
240
243
Chen
L.
,
Krause
M. W.
,
Sepanski
M.
,
Fire
A.
(
1994
)
The C. elegans MyoD homologue HLH-1 is essential for proper muscle function and complete morphogenesis.
Development
120
,
1631
1641
Cline
T. W.
(
1988
)
Evidence that sisterless-a and sisterless-b are two of several discrete ‘numerator elements’ of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states.
Genetics
119
,
829
862
Crittenden
S. L.
,
Troemel
E. R.
,
Evans
T. C.
,
Kimble
J.
(
1994
)
GLP-1 is localized to the mitotic region of the C. elegans germ line.
Development
120
,
2901
2911
Cronmiller
C.
,
Cline
T. W.
(
1986
)
The relationship of relative gene dose to the complex phenotype of the duaghterless locus in Drosophila.
Dev. Genet
7
,
205
221
Cronmiller
C.
,
Cline
T. W.
(
1987
)
The Drosophila sex determination gene daughterless has different functions in the germ line versus the soma.
Cell
48
,
479
487
Cronmiller
C.
,
Schedl
P.
,
Cline
T. W.
(
1988
)
Molecular characterization of daughterless, a Drosophila sex determination gene with multiple roles in development.
Genes Dev
2
,
1666
1676
Cronmiller
C.
,
Cummings
C. A.
(
1993
)
The daughterless gene product in Drosophila is a nuclear protein that is broadly expressed throughout the organism during development.
Mech. Dev
42
,
159
169
Cserjesi
P.
,
Brown
D.
,
Ligon
K. L.
,
Lyons
G. E.
,
Copeland
N. G.
,
Gilbert
D. J.
,
Jenkins
N. A.
,
Olson
E. N.
(
1995
)
Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embyrogenesis.
Development
121
,
1099
1110
Fitzgerald
K.
,
Greenwald
I.
(
1995
)
Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo.
Development
121
,
4275
4282
Fire
A.
,
Harrison
S. W.
,
Dixon
D. K.
(
1990
)
A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans.
Gene
93
,
189
198
Greenwald
I.
,
Rubin
G. M.
(
1992
)
Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells.
Cell
68
,
271
272
Guo
S.
,
Kemphues
K. J.
(
1995
)
par-1, a gene required for extablishing polarity in C. elegans embyros, encodes a putative Ser/Thr kinase that is asymmetically distributed.
Cell
81
,
611
620
Guo
S.
,
Kemphues
K. J.
(
1996
)
A non-muscle myosin required for embryonic polarity in Caenorhabditis elegans.
Nature
382
,
455
458
Henderson
S. T.
,
Gao
D.
,
Lambie
E. J.
,
Kimble
J.
(
1994
)
lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans.
Development
120
,
2913
2924
Henthorn
P.
,
Kiledjian
M.
,
Kadesch
T.
(
1990
)
Two transcription factors that bind the immunoglobulin enhancer μE5/kE2 motif.
Science
247
,
467
470
Hu
J.-S.
,
Olson
E. N.
,
Kingston
R. E.
(
1992
)
HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.
Mol. Cell. Biol
12
,
1031
1042
Ishibashi
M.
,
Ang
S. L.
,
Shiota
K.
,
Nakanishi
S.
,
Kageyama
R.
,
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
Jan
Y. N.
,
Jan
L. Y.
(
1993
)
HLH proteins, fly neurogenesis and vertebrate myogenesis.
Cell
75
,
827
830
Johnson
J. E.
,
Birren
S. J.
,
Anderson
D. J.
(
1990
)
Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors.
Nature
346
,
858
861
Krause
M. W.
,
Fire
A.
,
Harrison
S. W.
,
Priess
J.
,
Weintraub
H.
(
1990
)
CeMyoD accumulation defines the bodywall muscle cell fate during C. elegans embryogenesis.
Cell
63
,
907
922
Krause
M. W.
,
Hirsh
D.
(
1987
)
A trans-spliced leader sequence on actin mRNA in C. elegans.
Cell
49
,
753
761
Kunisch
M.
,
Haenlin
M.
,
Campos-Ortega
J. A.
(
1994
)
Lateral inhibition mediated by the Drosophila neurogenic gene Delta is enhanced by proneural proteins.
Proc. Nat. Acad. Sci. USA
91
,
10139
10143
Lambie
E. J.
,
Kimble
J.
(
1991
)
Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions.
Development
112
,
231
240
Lassar
A. B.
,
Buskin
J. N.
,
Lockshon
D.
,
Davis
R. L.
,
Apone
S.
,
Hauschka
S. D.
,
Weintraub
H.
(
1989
)
MyoD is a sequence-specificDNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer.
Cell
58
,
823
831
Lassar
A. B.
,
Davis
R. L.
,
Wright
W. E.
,
Kadesch
T.
,
Murre
C.
,
Voronova
A.
,
Baltimore
D.
,
Weintraub
H.
(
1991
)
Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo.
Cell
66
,
301
315
Li
L.
,
Cserjesi
P.
,
Olson
E. N.
(
1995
)
Dermo-1: A novel twist-related bHLH protein expressed in the developing dermis.
Dev. Biol
172
,
280
292
Lin
R. L.
,
Thompson
S.
,
Priess
J. R.
(
1995
)
pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos.
Cell
83
,
599
609
McCombie
W. R.
,
Adams
M. D.
,
Kelley
J. M.
,
Fitzgerald
M. G.
,
Utterback
T. R.
,
Khan
M.
,
Dubnick
M.
,
Kerlavage
A. R.
,
Venter
J. C.
,
Fields
C.
(
1992
)
Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues.
Nature Genetics
1
,
124
131
Murre
C.
,
McCaw
P. S.
,
Baltimore
D.
(
1989
)
A new DNA binding and dimerization motif in immunoglobulin enchancer binding, daughterless, MyoD, and myc proteins.
Cell
56
,
777
783
Murre
C.
,
McCaw
P. S.
,
Vaessin
H.
,
Caudy
M.
,
Jan
L. Y.
,
Jan
Y. N.
,
Cabrera
C. V.
,
Buskin
J. N.
,
Hauschka
S. D.
,
Lassar
A. B.
,
Weintraub
H.
,
Baltimore
D.
(
1989
)
Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.
Cell
58
,
537
544
Parkhurst
S. M.
,
Bopp
D.
,
Ish-Horowicz
D.
(
1990
)
X:A ratio, the primary sex-determining signal in Drosophila, is transduced by helix-loop-helix proteins.
Cell
63
,
1179
1191
Parkhurst
S. M.
,
Lipshitz
H. D.
,
Ish-Horowicz
D.
(
1993
)
achaete-scute feminizing activities and Drosophila sex determination.
Development
117
,
737
749
Shen
C.-P.
,
Kadesch
T.
(
1995
)
B-cell-specific DNA binding by an E47 homodimer.
Mol. Cell Biol
15
,
4518
4524
Shirakata
M.
,
Friedman
F. K.
,
Wei
Q.
,
Paterson
B. M.
(
1993
)
Dimerization specificity of myogenic helix-loop-helix DNA-binding factors directed by nonconserved hydrophilic residues.
Genes Dev
7
,
2456
2470
St Johnston
D.
,
Nusslein-Volhard
C.
(
1992
)
The origin of pattern and polarity in the Drosophila embryo.
Cell
68
,
201
219
Sultson
J. E.
,
Horvitz
H. R.
(
1977
)
Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
Dev. Biol
56
,
110
156
Sulston
J. E.
,
Schierenberg
E.
,
Thomson
J. N.
(
1983
)
The embryonic cell lineage of the nematode Caenorhabditis elegans.
Dev. Biol
100
,
64
119
Tabara
H.
,
Motohashi
T.
,
Kohara
Y.
(
1996
)
A multi-well version of in situ hybridization on whole mount embryos of Caenorhabditis elegans.
Nucleic Acids Res
24
,
2119
2124
Tax
F. E.
,
Yeargers
J. J.
,
Thomas
J. H.
(
1994
)
Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila.
Nature
368
,
150
154
Vaessin
H.
,
Brand
M.
,
Jan
L. Y.
,
Jan
Y. N.
(
1994
)
daughterless is essential for neuronal precursor differentiation but not for initiation of neuronal precursor formation in Drosophila embryo.
Development
120
,
935
945
Van Doren
M.
,
Ellis
H. M.
,
Posakony
J. W.
(
1991
)
The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless / achaete-scute protein complexes.
Development
113
,
245
255
Villares
R.
,
Cabrera
C. V.
(
1987
)
The achaete-scute gene complex of D. melanogaster: Conserved domains in a subset of genes required for neurogenesis and their homology to myc.
Cell
50
,
415
424
Waterston
R.
,
Sulston
J.
(
1995
)
The genome of Caenorhabditis elegans.
Proc. Nat. Acad. Sci. USA
92
,
10836
10840
Zhao
C.
,
Emmons
S. W.
(
1995
)
A transcription factor controlling development of peripheral sense organs in C. elegans.
Nature
373
,
74
78
Zhuang
Y.
,
Soriano
P.
,
Weintraub
H.
(
1994
)
The helix-loop-helix gene E2A is required for B cell formation.
Cell
79
,
875
884
This content is only available via PDF.