XB-ART-18864
Proc Natl Acad Sci U S A
December 19, 1995;
92
(26):
12141-5.
Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development.
Abstract
Bone morphogenetic protein 4 (
BMP-4) induces
ventral mesoderm but represses dorsal
mesoderm formation in Xenopus embryos. We show that
BMP-4 inhibits two signaling pathways regulating dorsal
mesoderm formation, the induction of dorsal
mesoderm (
Spemann organizer) and the dorsalization of
ventral mesoderm. Ectopic expression of
BMP-4 RNA reduces
goosecoid and forkhead-1 transcription in whole embryos and in activin-treated
animal cap explants. Embryos and animal caps overexpressing
BMP-4 transcribe high levels of genes expressed in
ventral mesoderm (
Xbra,
Xwnt-8,
Xpo,
Mix.1,
XMyoD). The
Spemann organizer is ventralized in these embryos; abnormally high levels of
Xwnt-8 mRNA and low levels of
goosecoid mRNA are detected in the
organizer. In addition, the
organizer loses the ability to dorsalize neighboring
ventral marginal zone to
muscle. Overexpression of
BMP-4 in
ventral mesoderm inhibits its response to dorsalization signals.
Ventral marginal zone explants ectopically expressing
BMP-4 form less
muscle when treated with soluble
noggin protein or when juxtaposed to a normal
Spemann organizer in comparison to control explants. Endogenous
BMP-4 transcripts are downregulated in
ventral marginal zone explants dorsalized by
noggin, in contrast to untreated explants. Thus, while
BMP-4 inhibits
noggin protein activity,
noggin downregulates
BMP-4 expression by dorsalizing
ventral marginal zone to
muscle.
Noggin and
BMP-4 activities may control the
lateral extent of dorsalization within the
marginal zone. Competition between these two molecules may determine the final degree of
muscle formation in the
marginal zone, thus defining the border between dorsolateral and
ventral mesoderm.
PubMed ID:
8618860
PMC ID:
PMC40312
Article link:
Proc Natl Acad Sci U S A
Species referenced:
Xenopus laevis
Genes referenced:
bmp4
gsc
mix1
myod1
nog
post
tbxt
wnt8a
xpo1
References [+] :
Amaya,
FGF signalling in the early specification of mesoderm in Xenopus.
1993,
Pubmed,
Xenbase
Amaya,
FGF signalling in the early specification of mesoderm in Xenopus.
1993,
Pubmed
,
Xenbase
Blumberg,
Organizer-specific homeobox genes in Xenopus laevis embryos.
1991,
Pubmed
,
Xenbase
Cambridge,
Mechanism of bradykinin-induced plasma extravasation in the rat knee joint.
1995,
Pubmed
Christian,
Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis.
1991,
Pubmed
,
Xenbase
Cooke,
Mesoderm-inducing factors and Spemann's organiser phenomenon in amphibian development.
1990,
Pubmed
,
Xenbase
Dale,
Regional specification within the mesoderm of early embryos of Xenopus laevis.
1987,
Pubmed
,
Xenbase
Dale,
Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development.
1992,
Pubmed
,
Xenbase
Dirksen,
A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.
1992,
Pubmed
,
Xenbase
Fainsod,
On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo.
1994,
Pubmed
,
Xenbase
Frank,
Transient expression of XMyoD in non-somitic mesoderm of Xenopus gastrulae.
1992,
Pubmed
,
Xenbase
Graff,
Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo.
1994,
Pubmed
,
Xenbase
Green,
The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.
1990,
Pubmed
,
Xenbase
Hogan,
Growth factors in development: the role of TGF-beta related polypeptide signalling molecules in embryogenesis.
1995,
Pubmed
,
Xenbase
Jones,
DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction.
1992,
Pubmed
,
Xenbase
Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase
Kimelman,
Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo.
1988,
Pubmed
,
Xenbase
Krieg,
The mRNA encoding elongation factor 1-alpha (EF-1 alpha) is a major transcript at the midblastula transition in Xenopus.
1989,
Pubmed
,
Xenbase
Köster,
Bone morphogenetic protein 4 (BMP-4), a member of the TGF-beta family, in early embryos of Xenopus laevis: analysis of mesoderm inducing activity.
1991,
Pubmed
,
Xenbase
Lamb,
Neural induction by the secreted polypeptide noggin.
1993,
Pubmed
,
Xenbase
Lyons,
The DVR gene family in embryonic development.
1992,
Pubmed
,
Xenbase
New,
Inductive interactions in early embryonic development.
1992,
Pubmed
,
Xenbase
Rosa,
Mix.1, a homeobox mRNA inducible by mesoderm inducers, is expressed mostly in the presumptive endodermal cells of Xenopus embryos.
1989,
Pubmed
,
Xenbase
Sato,
Localized and inducible expression of Xenopus-posterior (Xpo), a novel gene active in early frog embryos, encoding a protein with a 'CCHC' finger domain.
1991,
Pubmed
,
Xenbase
Schmidt,
Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo.
1995,
Pubmed
,
Xenbase
Sive,
The frog prince-ss: a molecular formula for dorsoventral patterning in Xenopus.
1993,
Pubmed
,
Xenbase
Smith,
Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction.
1991,
Pubmed
,
Xenbase
Smith,
Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
1991,
Pubmed
,
Xenbase
Smith,
Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.
1992,
Pubmed
,
Xenbase
Smith,
Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm.
1993,
Pubmed
,
Xenbase
Sokol,
A mouse macrophage factor induces head structures and organizes a body axis in Xenopus.
1990,
Pubmed
,
Xenbase
Stewart,
The anterior extent of dorsal development of the Xenopus embryonic axis depends on the quantity of organizer in the late blastula.
1990,
Pubmed
,
Xenbase
Taira,
The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.
1992,
Pubmed
,
Xenbase