Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Tbx5 is dispensable for forelimb outgrowth.
[holt-oram syndrome]
Tbx
5
is
essential
for
initiation
of
the
forelimb
,
and
its
deletion
in
mice
results
in
the
failure
of
forelimb
formation
.
Misexpression
of
dominant-negative
forms
of
Tbx
5
results
in
limb
truncations
,
suggesting
Tbx
5
is
also
required
for
forelimb
outgrowth
.
Here
we
show
that
Tbx
5
is
expressed
throughout
the
limb
mesenchyme
in
progenitors
of
cartilage
,
tendon
and
muscle
.
Using
a
tamoxifeninducible
Cre
transgenic
line
,
we
map
the
time
frame
during
which
Tbx
5
is
required
for
limb
development
.
We
show
that
deletion
of
Tbx
5
subsequent
to
limb
initiation
does
not
impair
limb
outgrowth
.
Furthermore
,
we
distinguish
two
distinct
phases
of
limb
development
:
a
Tbx
5
-
dependent
limb
initiation
phase
,
followed
by
a
Tbx
5
-
independent
limb
outgrowth
phase
.
In
humans
,
mutations
in
the
T
-
box
transcription
factor
TBX
5
are
associated
with
the
dominant
disorder
Holt-
Oram
syndrome
(
HOS
)
,
which
is
characterised
by
malformations
in
the
forelimb
and
heart
.
Our
results
demonstrate
a
short
temporal
requirement
for
Tbx
5
during
early
limb
development
,
and
suggest
that
the
defects
found
in
HOS
arise
as
a
result
of
disrupted
TBX
5
function
during
this
narrow
time
window
.