The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.

Reference

Adler
P. N.
(
1992
)
The genetic control of tissue polarity in Drosophila.
BioEssays
14
,
735
741
Bhanot
P.
,
Brink
M.
,
Samos
C. H.
,
Hsieh
J.
,
Wang
Y.
,
Macke
J. P.
,
Andrew
D.
,
Nathans
J.
,
Nusse
R.
(
1996
)
A new member of the frizzled family from Drosophila functions as a Wingless receptor.
Nature
382
,
225
230
Brannon
M.
,
Gomperts
M.
,
Sumoy
L.
,
Moon
R. T.
,
Kimelman
D.
(
1997
)
A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus.
Genes Dev
11
,
2359
2370
Brenner
S.
(
1974
)
The genetics of C. elegans.
Genetics
77
,
71
94
Cadigan
K. M.
,
Nusse
R.
(
1997
)
Wnt signaling: a common theme in animal development.
Genes Dev
11
,
3286
3305
Castelli-Gair
J.
,
Akam
M.
(
1995
)
How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres.
Development
121
,
2973
2982
Chisholm
A.
(
1991
)
Control of cell fate in the tail region of C. elegans by the gene egl-5.
Development
111
,
921
932
Clark
S. G.
,
Chisholm
A. D.
,
Horvitz
H. R.
(
1993
)
Control of cellfates in the central body region of C. elegans by the homeobox gene lin-39.
Cell
74
,
43
55
Costa
M.
,
Weir
M.
,
Coulson
A.
,
Sulston
J.
,
Kenyon
C.
(
1988
)
Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox.
Cell
55
,
747
756
Cowing
D. W.
,
Kenyon
C.
(
1992
)
Expression of the homeotic gene mab-5 during Caenorhabditis elegans embryogenesis.
Development
116
,
481
490
Desai
C.
,
Garriga
G.
,
McIntire
S. L.
,
Horvitz
H. R.
(
1988
)
A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons.
Nature
336
,
638
646
Eisenmann
D. M.
,
Maloof
J. N.
,
Simske
J. S.
,
Kenyon
C.
,
Kim
S. K.
(
1998
)
The-catenin homolog BAR-1 and LET-60 Rascoordinately regulate the Hox gene lin-39 during C. elegans vulval development.
Development
125
,
3667
3680
Ferguson
E. L.
,
Horvitz
H. R.
(
1985
)
Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans.
Genetics
110
,
17
72
Fire
A.
,
Harrison
S. W.
,
Dixon
D.
(
1990
)
A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans.
Gene
93
,
189
198
Frohman
M. A.
(
1993
)
Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE.
Meth. Enzymol
218
,
340
356
Gavin
B. J.
,
McMahon
J. A.
,
McMahon
A. P.
(
1990
)
Expression of multiple novel Wnt-1/int-1 -related genes during fetal and adult mouse development.
Genes Dev
4
,
2319
2332
Han
M.
(
1997
)
Gut reaction to Wnt signaling in worms [comment].
Cell
90
,
581
584
Harris
J.
,
Honigberg
L.
,
Robinson
N.
,
Kenyon
C.
(
1996
)
Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position.
Development
122
,
3117
3131
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
Herman
M. A.
,
Vassilieva
L. L.
,
Horvitz
H. R.
,
Shaw
J. E.
,
Herman
R. K.
(
1995
)
The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously.
Cell
83
,
101
110
Kenyon
C.
(
1986
)
A gene involved in the development of the posterior body region of C. elegans.
Cell
46
,
477
487
Maloof
J. N.
,
Kenyon
C.
(
1998
)
The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling.
Development
125
,
181
190
Mello
C. C.
,
Kramer
J. M.
,
Stinchcomb
D.
,
Ambros
V.
(
1991
)
Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences.
EMBO J
10
,
3959
3970
Miller
J. R.
,
Moon
R. T.
(
1996
)
Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
Genes Dev
10
,
2527
2539
Munemitsu
S.
,
Albert
I.
,
Souza
B.
,
Rubinfeld
B.
,
Polakis
P.
(
1995
)
Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
Proc. Natl. Acad. Sci. USA
92
,
3046
3050
Nelson
C. E.
,
Morgan
B. A.
,
Burke
A. C.
,
Laufer
E.
,
DiMambro
E.
,
Murtaugh
L. C.
,
Gonzales
E.
,
Tessarollo
L.
,
Parada
L. F.
,
Tabin
C.
(
1996
)
Analysis of Hox gene expression in the chick limb bud.
Development
122
,
1449
1466
Nusse
R.
(
1997
)
A versatile transcriptional effector of Wingless signaling.
Cell
89
,
321
323
Orsulic
S.
,
Peifer
M.
(
1996
)
An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling.
J. Cell Biol
134
,
1283
1300
Pai
L. M.
,
Orsulic
S.
,
Bejsovec
A.
,
Peifer
M.
(
1997
)
Negative regulation of Armadillo, a Wingless effector in Drosophila.
Development
124
,
2255
2266
Peifer
M.
,
Sweeton
D.
,
Casey
M.
,
Wieschaus
E.
(
1994
)
wingless signal and Zeste-white 3 kinase trigger opposing changes in intracellular distribution of Armadillo.
Development
120
,
369
380
Pirrotta
V.
(
1997
)
PcG complexes and chromatin silencing.
Curr. Opin. Genet. Dev
7
,
249
258
Polakis
P.
(
1997
)
The adenomatous polyposis coli (APC) tumor suppressor.
Biochim. Biophys. Acta
1332
,
127
147
Rijsekijk
F.
,
Schuermann
M.
,
Wagenaar
E.
,
Parren
P.
,
Weigel
D.
,
Nusse
R.
(
1987
)
The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless.
Cell
50
,
649
657
Rocheleau
C. E.
,
Downs
W. D.
,
Lin
R.
,
Wittmann
C.
,
Bei
Y.
,
Cha
Y. H.
,
Ali
M.
,
Priess
J. R.
,
Mello
C. C.
(
1997
)
Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos [see comments].
Cell
90
,
707
716
Rubinfeld
B.
,
Albert
I.
,
Porfiri
E.
,
Fiol
C.
,
Munemitsu
S.
,
Polakis
P.
(
1996
)
Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly [see comments].
Science
272
,
1023
1026
Salser
S. J.
,
Kenyon
C.
(
1992
)
Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration.
Nature
355
,
2558
–.
Salser
S. J.
,
Kenyon
C.
(
1996
)
A C. elegans Hox gene switches on, off, on and off again to regulate proliferation, differentiation and morphogenesis.
Development
122
,
1651
1661
Sawa
H.
,
Lobel
L.
,
Horvitz
H. R.
(
1996
)
The Caenorhabditis elegans gene lin-17, which is required for certain asymmetric cell divisions, encodes a putative seven-transmembrane protein similar to the Drosophila frizzled protein.
Genes Dev
10
,
2189
2197
Siegfried
E.
,
Chou
T. B.
,
Perrimon
N.
(
1992
)
Wingless signaling acts through zeste-white 3, the Drosophila homolog glycogen synthase kinase-3, to regulate engrailed and establish cell fate.
Cell
71
,
1167
1179
Strome
S.
,
Garvin
C.
,
Paulsen
J.
,
Capowski
E.
,
Martin
P.
,
Beanan
M.
(
1994
)
Specification and development of the germline in Caenorhabditis elegans.
Ciba Foundation Symp
182
,
31
45
Thorpe
C. J.
,
Schlesinger
A.
,
Carter
J. C.
,
Bowerman
B.
(
1997
)
Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm [see Comments].
Cell
90
,
695
705
Trent
C.
,
Tsung
N.
,
Horvitz
H.
(
1983
)
Egg-laying defective mutants of the nematode C. elegans.
Genetics
104
,
619
647
van de Wetering
M.
,
Cavallo
R.
,
Dooijes
D.
,
van Beest
M.
,
van Es
J.
,
Loureiro
J.
,
Ypma
A.
,
Hursh
D.
,
Jones
T.
,
Bejsovec
A.
,
Peifer
M.
,
Mortin
M.
,
Clevers
H.
(
1997
)
Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.
Cell
88
,
789
799
von Heijne
(
1986
)
Net N-C charge imbalance may be important for signal sequence function in bacteria.
J. Mol. Biol
192
,
287
290
Wang
B. B.
,
Muller
I. M.
,
Austin
J.
,
Robinson
N. T.
,
Chisholm
A.
,
Kenyon
C.
(
1993
)
A homeotic gene cluster patterns the anteroposterior body axis of C. elegans.
Cell
74
,
29
42
Williams
B. D.
,
Schrank
B.
,
Huynh
C.
,
Shownkeen
R.
,
Waterston
R. H.
(
1992
)
A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites.
Genetics
131
,
609
624
Wrischnik
L. A.
,
Kenyon
C. J.
(
1997
)
The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.
Development
124
,
2875
2888
Zeng
L.
,
Fagotto
F.
,
Zhang
T.
,
Hsu
W.
,
Vasicek
T. J.
,
Perry
W. R.
,
Lee
J. J.
,
Tilghman
S. M.
,
Gumbiner
B. M.
,
Costantini
F.
(
1997
)
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
Cell
90
,
181
192
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