Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis. Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut.

Reference

Biben
C.
,
Harvey
R. P.
(
1997
)
Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHAND during murine heart development.
Genes Dev
11
,
1357
1369
Blum
M.
,
Gaunt
S. J.
,
Cho
K. W. Y.
,
Steinbeisser
H.
,
Blumberg
B.
,
Bittner
D.
,
De Robertis
E. M.
(
1992
)
Gastrulation in the mouse: the role of the homeobox gene goosecoid.
Cell
69
,
1097
1106
Chalmers
A. D.
,
Slack
J. M. W.
(
1998
)
Development of the gut in Xenopus laevis.
Dev. Dyn
212
,
509
521
Cleaver
O. B.
,
Patterson
K. D.
,
Krieg
P. A.
(
1996
)
Overexpression of the tinman-related genes Xnkx2. 5 and Xnkx-2. 3 in Xenopus embryos results in myocardial hyperplasia.
Development
122
,
3549
3556
Collignon
J.
,
Varlet
I.
,
Robertson
E. J.
(
1996
)
Relationship between asymmetric nodal expression and the direction of embryonic turning.
Nature
381
,
155
158
Danos
M. C.
,
Yost
H. J.
(
1996
)
Role of notochord in specification of cardiac left-right orientation in zebrafish and Xenopus.
Dev. Biol
177
,
96
103
Ding
X.
,
Hausen
P.
,
Steinbeisser
H.
(
1998
)
Pre-MBT patterning of early gene regulation in Xenopus: the role of the cortical rotation and mesoderm induction.
Mech Dev
70
,
15
24
Drysdale
T. A.
,
Tonissen
K. F.
,
Patterson
K. D.
,
Crawford
M. J.
,
Krieg
P. A.
(
1994
)
Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis.
Dev. Biol
165
,
432
441
Enbom
G.
(
1939
)
The early looping of the alimentary canal in the mammalian and human foetus and the mechanisms assumed to be active in this process.
Anat Rec
75
,
409
414
Gage
P. J.
,
Camper
S. A.
(
1997
)
Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation.
Hum. Mol. Gen
6
,
457
464
Hanes
S. D.
,
Brent
R.
(
1989
)
DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9.
Cell
57
,
1275
1283
Hummel
K. P.
,
Chapman
D. B.
(
1959
)
Visceral inversion and associated anomalies in the mouse.
J. Hered
50
,
9
13
Hyatt
B. A.
,
Yost
H. J.
(
1998
)
The left-right coordinator: the role of Vg1 in organizing left-right axis formation.
Cell
93
,
37
46
Isaac
A.
,
Sargent
M. G.
,
Cooke
J.
(
1997
)
Control of vertebrate left-right asymmetry by a snail-related zinc finger gene.
Science
275
,
1301
1304
Itasaki
N.
,
Nakamura
H.
,
Yasuda
M.
(
1989
)
Changes in the arrangment of actin bundles during heart looping in the chick embryo.
Anat. Embryol
180
,
413
420
Itasaki
N.
,
Nakamura
H.
,
Sumida
H.
,
Yasuda
M.
(
1991
)
Actin bundles on the right side in the caudal part of the heart tube play a role indextro-looping in the embryonic chick heart.
Anat. Embryol
183
,
29
39
Jones
C. M.
,
Kuehn
M. R.
,
Hogan
B. L. M.
,
Smith
J. C.
,
Wright
C. V. E.
(
1995
)
Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation.
Development
121
,
3651
3662
Jorgenson
R. J.
,
Levin
L. S.
,
Cross
H. E.
,
Yoder
F.
,
Kelly
T. E.
(
1978
)
The Rieger syndrome.
Am. J. Med. Genet
2
,
307
318
King
T.
,
Brown
N. A.
(
1997
)
Embryonic asymmetry: left TGFB at the right time?.
Curr. Biol
7
,
212
215
Kitamura
K.
,
Miura
H.
,
Yanazawa
M.
,
Miyashita
T.
,
Kato
K.
(
1997
)
Expression pattern of Brx1 (Rieg gene), Sonic hedgehog, Nk2. 2, Dlx1 and Arx during zona limithans intrathalamica and embryonic ventral lateral geniculate nuclear formation.
Mech. Dev
67
,
83
96
Kulharya
A. S.
,
Maberry
M.
,
Kukolich
M. K.
,
Day
D. W.
,
Schneider
N. R.
,
Wilson
G. N.
,
Tonk
V.
(
1995
)
Interstitial deletions 4q21. 1q25and 4q25q27: phenotipic variability and relation to Rieger anomaly.
Am. J. Med. Gen
55
,
165
170
Lamonerie
T.
,
Tremblay
J. J.
,
Lanctot
C.
,
Therrien
M.
,
Gauthire
Y.
,
Drouin
J.
(
1996
)
Ptx1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene.
Genes Dev
10
,
1284
1295
Lohr
J. L.
,
Danos
M. C.
,
Yost
H. J.
(
1997
)
Left-right asymmetry of a nodal-related gene is regulated by dorsoanterior midline structures during Xenopus development.
Development
124
,
1465
1472
Logan
M.
,
Pagan-Westphal
S. M.
,
Smith
D. M.
,
Paganessi
L.
,
Tabin
C. J.
(
1998
)
The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetricc signals.
Cell
94
,
307
317
Levin
M.
,
Johnson
R.
,
Stern
C.
,
Kuehn
M.
,
Tabin
C.
(
1995
)
A molecular pathway determining left-right asymmetry in chick embryogenesis.
Cell
82
,
803
814
Levin
M.
,
Pagan
S.
,
Roberts
D. J.
,
Cooke
J.
,
Kuehn
M. R.
,
Tabin
C. J.
(
1997
)
Left/right patterning signals and the independent regulation of different aspects of situs in the chick embryo.
Dev. Biol
189
,
57
67
Lowe
L. A.
,
Supp
D. M.
,
Sampath
K.
,
Yokoyama
T.
,
Wright
C. W.
,
Potter
S. S.
,
Overbeek
P.
,
Kuehn
M. R.
(
1996
)
Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus.
Nature
381
,
158
161
Meno
C.
,
Saijoh
Y.
,
Fujii
H.
,
Ikeda
M.
,
Yokoyama
T.
,
Yokoyama
M.
,
Toyoda
Y.
,
Hamada
H.
(
1996
)
Left-right asymmetric expression ofthe TGF-family member lefty in mouse embryos.
Nature
381
,
151
155
Meno
C.
,
Shimono
A.
,
Saijoh
Y.
,
Yashiro
K.
,
Mochida
K.
,
Oishi
S.
,
Noji
S.
,
Kondoh
H.
,
Hamada
H.
(
1998
)
lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal.
Cell
94
,
287
297
Mucchielli
M.-l.
,
Martinez, Salvador
,
Pattyn
A.
,
Godiris
C.
,
Brunet
J.-F.
(
1996
)
Otlx2, an otx-related homeobox gene expressed in the pituitary gland and in a restricted pattern in the forebrain.
Mol. Cell. Neurosc
8
,
252
271
Nascone
N.
,
Mercola
M.
(
1997
)
Organizer induction determines left-right asymmetry in Xenopus.
Dev. Biol
189
,
68
78
Pagan-Westphal
S. M.
,
Tabin
C. J.
(
1998
)
The transfer of left-right positional information during chick embryogenesis.
Cell
93
,
25
35
Piedra
M. E.
,
Icaardo
J. M.
,
Albajar
M.
,
Rodriguez-Rey
J. C.
,
Ros
M. A.
(
1998
)
Pitx2 participates in the late phase of the pathway controlling left-right asymmetry.
Cell
94
,
319
324
Rupp
R. A. W.
,
Snider
L.
,
Weintraub
H.
(
1994
)
Xenopus embryos regulate the nuclear organization of XMyoD.
Genes Dev
8
,
1311
1323
Ryan
A. K.
,
Blumberg
B.
,
Rodriguez-Esteban
C.
,
Yonei-Tamura
S.
,
Tamura
K.
,
Tsukui
T.
,
de la Pena
J.
,
Sabbagh
W.
,
Greenwald
J.
,
Choe
S.
,
Norris
D. P.
,
Robertson
E. J.
,
Evans
R. M.
,
Rosenfeld
M. R.
,
Izpisua-Belmonte
J. C.
(
1998
)
Pitx2 determines left-right asymmetry of internal organs in vertebrates.
Nature
394
,
545
551
Sampath
K.
,
Cheng
A. M. S.
,
Frisch
A.
,
Wright
C. V. E.
(
1997
)
Functional differences among Xenopus nodal-related genes in left-right axis determination.
Development
124
,
3293
3302
Schaart
G.
,
Viebahn
C.
,
Langmann
W.
,
Ramaekers
F. C. S.
(
1989
)
Desmin and titin expression in early postimplantation mouse embryos.
Development
107
,
585
596
Semina
E. V.
,
Reiter
R.
,
Leysens
N. J.
,
Alward
W. L. M.
,
Small
K. W.
,
Datson
N. A.
,
Siegel-Bartelt
J.
,
Bierke-Nelson
D.
,
Bitoun
P.
,
Zabel
B. U.
,
Carey
J. C.
,
Murray
J. C.
(
1996
)
Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome.
Nat. Genet
14
,
392
399
Sparrow
D. B.
,
Kotecha
S.
,
Towers
N.
,
Mohun
T. J.
(
1998
)
Xenopus eHAND: a marker for the developing cardiovascular system of the embryo is regulated by bone morphogenetic proteins.
Mech Dev
71
,
151
163
Srivastava
D.
,
Cserjesi
P.
,
Olson
E. N.
(
1995
)
A subclass of bHLH proteins required for cardiac morphogenesis.
Science
270
,
1995
1999
Stalsberg
H.
(
1969
)
The origin of heart asymmetry: Right and left contributions to the early chick embryo heart.
Dev. Biol
19
,
109
129
Tsuda
T.
,
Philp
N.
,
Zile
J. K.
,
Linask
K. K.
(
1996
)
Left-right asymmetric location of flectin in the extracellular matrix during heart looping.
Dev. Biol
173
,
39
50
Vorbruggen
G.
,
Constien
R.
,
Zilian
O.
,
Wimmer
E. A.
,
Dowe
G.
,
Taubert
H.
,
Noll
M.
,
Jäckle
H.
(
1997
)
Embryonic expressionandcharacterization of a Ptx1 homolog in Drosophila.
Mech. Dev
68
,
139
147
Yoshioka
H.
,
Meno
C.
,
Koshiba
K.
,
Sugihara
M.
,
Itoh
H.
,
Ishimura
Y.
,
Inoue
T.
,
Ohuchi
H.
,
Semina
E.
,
Murray
J. C.
,
Hamada
H.
,
Noji
S.
(
1998
)
Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry.
Cell
94
,
299
305
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