Articles
Wnt
- Wnt signalling required for expansion of neural
crest and CNS progenitors. Nature 1997 Oct
30;389(6654):966-70 Ikeya M, Lee SM, Johnson JE, McMahon
AP, Takada S Centre for Molecular and Developmental
Biology, Faculty of Science, Kyoto University, Japan.
- Interactions between cells help to elaborate
pattern within the vertebrate central nervous system
(CNS). The genes Wnt-1 and Wnt-3a, which encode
members of the Wnt family of cysteine-rich secreted
signals, are coexpressed at the dorsal midline of the
developing neural tube, coincident with dorsal
patterning. Each signal is essential for embryonic
development, Wnt-1 for midbrain patterning, and Wnt-3a
for formation of the paraxial mesoderm, but the
absence of a dorsal neural-tube phenotype in each
mutant suggests that Wnt signalling may be redundant.
Here we demonstrate that in the absence of both Wnt-
and Wnt-3a there is a marked deficiency in neural
crest derivatives, which originate from the dorsal
neural tube, and a pronounced reduction in
dorsolateral neural precursors within the neural tube
itself. These phenotypes do not seem to result from a
disruption in the mechanisms responsible for
establishing normal dorsoventral polarity. Rather, our
results are consistent with a model in which local Wnt
signalling regulates the expansion of dorsal neural
precursors. Given the widespread expression of
different Wnt genes in discrete areas of the mammalian
neural tube, this may represent a general model for
the action of Wnt signalling in the developing
CNS.
- Dorsalization of the neural tube by the non-neural
ectoderm. Dickinson ME, Selleck MA, McMahon AP,
Bronner-Fraser M Development 1995 Jul;121(7):2099-106
- The patterning of cell types along the
dorsoventral axis of the spinal cord requires a
complex set of inductive signals. While the
chordamesoderm is a well-known source of ventralizing
signals, relatively little is known about the cues
that induce dorsal cell types, including neural crest.
Here, we demonstrate that juxtaposition of the
non-neural and neural ectoderm is sufficient to induce
the expression of dorsal markers, Wnt-1, Wnt-3a and
Slug, as well as the formation of neural crest cells.
In addition, the competence of neural plate to express
Wnt-1 and Wnt-3a appears to be stage dependent,
occurring only when neural tissue is taken from stage
8-10 embryos but not from stage 4 embryos, regardless
of the age of the non-neural ectoderm. In contrast to
the induction of Wnt gene expression, neural crest
cell formation and Slug expression can be induced when
either stage 4 or stage 8-10 neural plates are placed
in contact with the non-neural ectoderm. These data
suggest that the non-neural ectoderm provides a signal
(or signals) that specifies dorsal cell types within
the neural tube, and that the response is dependent on
the competence of the neural tissue.
- Identification of an evolutionarily conserved 110
base-pair cis-acting regulatory sequence that governs
Wnt-1 expression in the murine neural plate. Development
1998 Jul;125(14):2735-46 Rowitch DH, Echelard Y,
Danielian PS, Gellner K, Brenner S, McMahon AP
- The generation of anterior-posterior polarity in
the vertebrate brain requires the establishment of
regional domains of gene expression at early somite
stages. Wnt-1 encodes a signal that is expressed in
the developing midbrain and is essential for midbrain
and anterior hindbrain development. Previous work
identified a 5.5 kilobase region located downstream of
the Wnt-1 coding sequence which is necessary and
sufficient for Wnt-1 expression in vivo. Using a
transgenic mouse reporter assay, we have now
identified a 110 base pair regulatory sequence within
the 5.5 kilobase enhancer, which is sufficient for
expression of a lacZ reporter in the approximate Wnt-1
pattern at neural plate stages. Multimers of this
element driving Wnt-1 expression can partially rescue
the midbrain-hindbrain phenotype of Wnt-1(-/-)
embryos. The possibility that this region represents
an evolutionarily conserved regulatory module is
suggested by the identification of a highly homologous
region located downstream of the wnt-1 gene in the
pufferfish (Fugu rubripes). These sequences are
capable of appropriate temporal and spatial activation
of a reporter gene in the embryonic mouse midbrain;
although, later aspects of the Wnt-1 expression
pattern are absent. Genetic evidence has implicated
Pax transcription factors in the regulation of Wnt-1.
Although Pax-2 binds to the 110 base pair murine
regulatory element in vitro, the location of the
binding sites could not be precisely established and
mutation of two putative low affinity sites did not
abolish activation of a Wnt-1 reporter transgene in
vivo. Thus, it is unlikely that Pax proteins regulate
Wnt-1 by direct interactions with this cis-acting
regulatory region. Our analysis of the 110 base pair
minimal regulatory element suggests that Wnt-1
regulation is complex, involving different regulatory
interactions for activation and the later maintenance
of transgene expression in the dorsal midbrain and
ventral diencephalon, and at the midbrain-hindbrain
junction.
Other neural plate issues
- Establishment and maintenance of the border of the
neural plate in the chick: involvement of FGF and BMP
activity. Streit A, Stern CD Mech Dev 1999
Apr;82(1-2):51-66 Abstract
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- MH- A related issue about how the neural plate may
be established and maintained.
- FGF = fibroblast growth factor
- BMP = bone morphogenic protein
- An early phase of embryonic Dlx5
expression defines the rostral boundary of the neural
plate. Yang L, Zhang H, Hu G, Wang H, Abate-Shen C,
Shen MM J Neurosci 1998 Oct 15;18(20):8322-30 Abstract
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- MH- A related issue about how the rostral end of
the neural plate may be defined.
- Dlx = Distal-less, a homeobox gene
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