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Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.
[kallmann syndrome]
New
subventricular
zone
(
SVZ
)
-
derived
neuroblasts
that
migrate
via
the
rostral
migratory
stream
are
continuously
added
to
the
olfactory
bulb
(
OB
)
of
the
adult
rodent
brain
.
Anosmin-
1
(
A
1
)
is
an
extracellular
matrix
protein
that
binds
to
FGF
receptor
1
(
FGFR
1
)
to
exert
its
biological
effects
.
When
mutated
as
in
Kallmann
syndrome
patients
,
A
1
is
associated
with
severe
OB
morphogenesis
defects
leading
to
anosmia
and
hypogonadotropic
hypogonadism
.
Here
,
we
show
that
A
1
over-expression
in
adult
mice
strongly
increases
proliferation
in
the
SVZ
,
mainly
with
symmetrical
divisions
,
and
produces
substantial
morphological
changes
in
the
normal
SVZ
architecture
,
where
we
also
report
the
presence
of
FGFR
1
in
almost
all
SVZ
cells
.
Interestingly
,
for
the
first
time
we
show
FGFR
1
expression
in
the
basal
body
of
primary
cilia
in
neural
progenitor
cells
.
Additionally
,
we
have
found
that
A
1
over-expression
also
enhances
neuroblast
motility
,
mainly
through
FGFR
1
activity
.
Together
,
these
changes
lead
to
a
selective
increase
in
several
GABAergic
interneuron
populations
in
different
OB
layers
.
These
specific
alterations
in
the
OB
would
be
sufficient
to
disrupt
the
normal
processing
of
sensory
information
and
consequently
alter
olfactory
memory
.
In
summary
,
this
work
shows
that
FGFR
1
-
mediated
A
1
activity
plays
a
crucial
role
in
the
continuous
remodelling
of
the
adult
OB
.
Diseases
Validation
Diseases presenting
"and produces substantial morphological changes in the normal svz architecture"
symptom
kallmann syndrome
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