Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development. Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo. In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Bmp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation. Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut. Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development). Using virally mediated misexpression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Hoxd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions. The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype. Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning. Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms.

Reference

Ang
S.-L.
,
Wierda
A.
,
Wong
D.
,
Stevens
K. A.
,
Cascio
S.
,
Rossant
J.
,
Zaret
K. S.
(
1993
)
, The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/ forkhead proteins.
Development
119
,
1301
1305
Basler
K.
,
Edlund
T.
,
Jessell
T. M.
,
Yamada
T.
(
1993
)
Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF -.
Cell
73
,
687
702
Basler
K.
,
Struhl
K.
(
1994
)
Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
Nature
368
,
208
14
Burke
A. C.
,
Nelson
C. E.
,
Morgan
B. M.
,
Tabin
C.
(
1995
)
Hox genes and the evolution of vertebrate axial morphology.
Development
121
,
333
346
Diaz-Benjumea
F. J.
,
Cohen
B.
,
Cohen
S. M.
(
1994
)
Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs.
Nature
372
,
175
179
Doctor
J. S.
,
Jackson
P. D.
,
Rashka
K. E.
,
Visalli
M.
,
Hoffmann
F. M.
(
1992
)
Sequence, biochemical characterization, and developmental expression of a new member of the TGF-superfamily in Drosophila melanogaster.
Dev. Biol.,
151
,
491
505
Dolle
P.
,
Izpisua-Belmonte
J. C.
,
Falkenstein
H.
,
Renucci
A.
,
Duboule
D.
(
1989
)
Coordinate expression of the murine Hox-5 complex-homeobox containing genes during limb pattern formation.
Nature
342
,
767
772
Dolle
P.
,
Izpisua-Belmonte
J. C.
,
Brown
J. M.
,
Tickle
C.
,
Duboule
D.
(
1991
)
HOX-4 genes and the morphogenesis of mammalian genitalia.
Genes Dev
5
,
1767
1776
Dolle
P.
,
Dierich
A.
,
LeMeur
M.
,
Schimmang
T.
,
Schuhbaur
B.
,
Chambon P and Duboule
D.
(
1993
)
Disruption of the Hoxd13 gene induces localized heterchrony leading to mice with neotenic limbs.
Cell
75
,
431
441
Echelard
Y.
,
Epstein
D. J.
,
St-Jacques
B.
,
Shen
L.
,
Mohler
J.
,
McMahon
J. A.
,
McMahan
A.
(
1993
)
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity.
Cell
75
,
1417
1430
Fan
C.-M.
,
Tessier-Lavigne
M.
(
1994
)
Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.
Cell
79
,
1175
1186
Francis
P. H.
,
Richardson
M. K.
,
Brickell
P. M.
,
Tickle
C.
(
1994
)
Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb.
Development
120
,
209
218
Haffen
K.
,
Lacroix
B.
,
Kedinger
M.
,
Simon-Assmann
P. M.
(
1983
)
Inductive properties of fibroblastic cell cultures derived from rat intestinal mucosa on epithelial differentiation.
Differentiation
23
,
226
233
Haffen
K.
,
Kedinger
M.
,
Simon-Assman
P.
(
1987
)
Mesenchyme-dependent differentiation of epithelial progenitor cells in the gut. J. Pediat. Gastroenterol.
Nutr
6
,
14
23
Hamburger
V.
,
Hamilton
H. L.
(
1951
)
A series of normal stages in the development of the chick embryo.
J. Exp. Morph
88
,
49
92
Heberlein
U.
,
Wolff
T.
,
Rubin
G. M.
(
1993
)
The TGF- homolog and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina.
Cell
75
,
913
926
Hornbruch
A.
,
Wolpert
L.
(
1986
)
Positional signalling by Hensen's node when grafted to the chick limb bud.
J. Embryol. Exp. Morph
94
,
257
265
Immergluck
K.
,
Lawrence
P. A.
,
Bienz
M.
(
1990
)
Induction across germ layers in Drosophila mediated by a genetic cascade.
Cell
62
Ishizuya-Oka
A.
,
Mizuno
T.
(
1984
).
Intestinal cytodifferentiation in vitro of chick stomach endoderm induced by the duodenal mesenchyme.
J. Embryol. Exp. Morph
82
,
163
176
Izpisua-Belmonte
J. C.
,
Tickle
C.
,
Dolle
P.
,
Wolpert
L.
,
Duboule
D.
(
1991
)
Expression of the homeobox Hox-4 genes and the specification of position in chick wing development.
Nature
350
,
585
589
Izpisua-Belmonte
J. C.
,
Falkenstein
H.
,
Dolle
P.
,
Tenucci
A.
,
Duboule
D.
(
1991
)
Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body.
EMBO J
10
,
2279
2289
Johnson
R. L.
,
Laufer
E.
,
Riddle
R. D.
,
Tabin
C.
(
1994
)
Ectopicexpression of Sonichedgehog alters dorsal-ventral patterning of somites.
Cell
79
,
1165
1173
Kedinger
M.
,
Simon-Assmann
P. M.
,
Lacroix
B.
,
Marxer
A.
,
Hauri
H. P.
,
Haffen
K.
(
1986
)
Fetal gut mesenchyme induces differentiation of cultured intestinal endodermal and crypt cells.
Dev. Biol
113
,
474
483
Kedinger
M.
,
Simon-Assmann
P. M.
,
Bouziges
F.
,
Arnold
C.
,
Alexandre
E.
,
Haffen
K.
(
1990
)
Smooth muscle actin expression during rat gut development and induction in fetal skin fibroblastic cells associated with intestinal embryonic epithelium.
Differentiation
43
,
87
97
Kraus
S.
,
Concordet
J.-P.
,
Ingham
P. W.
(
1994
)
A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizaing activity in zebrafish embryos.
Cell,
75
,
1437
1444
Krumlauf
R.
(
1994
)
Hox genes in vertebrate development.
Cell
78
,
191
201
Laufer
E.
,
Nelson
C. E.
,
Johnson
R. L.
,
Morgan
B. A.
,
Tabin
C.
(
1994
)
Sonic hedgehog and FGF-4 act through a signaling cascade and feedback loop to integrate growth and patterning on the developing limb bud.
Cell
79
,
993
1003
Lee
J. J.
,
Ekker
S. C.
,
von Kessler
D. P.
,
Porter
J. A.
,
Sun
B. I.
,
Beachy
P. A.
(
1994
)
Autoproteolysis in hedgehog protein biogenesis.
Science
266
,
1528
1537
Ma
C.
,
Zhou
Y.
,
Beachy
P. A.
,
Moses
K.
(
1993
).
. The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye.
Cell
75
,
913
926
McGinnis
W.
,
Krumlauf
R.
(
1992
)
Homeobox genes and axial patterning.
Cell
68
,
283
302
Mohler
J.
,
Vani
K.
(
1992
)
Molecular organization and embyronic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila.
Development
115
,
957
971
Monaghan
A. P.
,
Kaustner
K. H.
,
Grau
E.
,
Schutz
G.
(
1993
)
Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 andgenes in determination of the definitive endoderm, chordamesoderm, and neuroectoderm.
Development
119
,
567
578
New
D. A. T.
(
1955
)
A new technique for the cultivation of the chick embryo in vitro.
J. Embryol. Exp. Morph
3
,
320
331
Nohno
T.
,
Noji
S.
,
Koyama
S.
,
Ohyama
K.
,
Myokai
F.
,
Kuroiwa
A.
,
Saito
T.
,
Taniguchi
S.
(
1991
)
Involvement of the Chox-4 chicken homeobox benes in determination of anteroposterior axial polarity during limb development.
Cell
64
,
1197
1205
Panganiban
G. F.
,
Reuter
R.
,
Scott
M. P.
,
Hoffmann
F. M.
(
1990
)
A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis.
Development
100
,
1041
1050
Pollock
R. A.
,
Jay
G.
,
Bieberich
C. J.
(
1992
)
, Altering the boundaries of Hox3. 1 expression: Evidence for antipodal gene regulation.
Cell
71
,
911
923
Riddle
R. D.
,
Johnson
R. L.
,
Laufer
E.
,
Tabin
C.
(
1993
)
Sonic hedgehog mediates the polarizing activity of the ZPA.
Cell
75
,
1401
1416
Roelink
H.
,
Augsburger
A.l.
,
Heemskerk
J.
,
Korzh
V.
,
Norlin
S.
,
Ruiz i Altaba
A.
,
Tanabe
Y.
,
Placzek
M.
,
Edlund
T.
,
Jessel
T. M.
,
Dodd
J.
(
1994
).
. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord.
Cell
76
,
761
775
Sasaki
H.
,
Hogan
B. L. M.
(
1994
)
, HNF-3 as a regulator of floor plate development.
Cell
76
,
103
115
Staehling-Hampton
K.
,
Hoffmann
F. M.
,
Baylies
M. K.
,
Rushton
E.
,
Bate
M.
(
1994
)
dpp induces mesodermal gene expression in Drosphila.
Nature
372
,
783
786
Staehling-Hampton
K.
,
Hoffman
F. M.
(
1994
)
, Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects.
Dev. Biol
154
,
502
512
Tabata
T.
,
Kornberg
T. B.
(
1994
)
Hedghog is a signaling protein with a key role in patterning Drosophila imaginal discs.
Cell
76
,
89
102
Taylor
A. M.
,
Nakano
Y.
,
Mohler
J.
,
Ingham
P. W.
(
1993
)
Contrasting distributions of patched and hedgehog proteins in the Drosophila embryo.
Mech. Dev
42
,
89
96
Tremml
G.
,
Bienz
M.
(
1989
)
Homeotic gene expression in the visceral mesoderm of Drosophila embryos.
EMBO J
8
,
2677
2685
Wagner
M.
,
Thaller
C.
,
Jessell
T.
,
Eichele
G.
(
1990
)
Polarizingactivity and retinoid synthesis in the floor plate of the neural tube.
Nature
345
,
819
822
Wharton
J. M.
,
Thomsen
G. H.
,
Gelbart
W. M.
(
1991
)
Drosophila 60A gene, a new tranforming growth factorfamily member, is closely related to human bone morphogenetic proteins.
Proc. Natl. Acad. Sci. USA
88
,
9214
9218
Yasugi
S.
(
1984
)
Differentiation of allantoic endoderm implanted into the presumptive digestive area in avian embryos. A study with organ-specific antigens.
J. Embryol. Exp. Morph
80
,
137
153
Yokouchi
Y.
,
Sakiyama
J.
,
Kuroiwa
A.
(
1995
)
Coordinated expression of Abd-B subfamily genes of the HoxA cluster in the developoing digestive tract of chick embryo.
Dev. Biol
169
,
76
89
This content is only available via PDF.