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V2
interneuron development is regulated by multiple Delta-Notch signaling
○ Sayumi
Okigawa 1,
Miho Isoda 1,
Maximiliano Suster 3,
Hiroshi Kikuta 3,
Koichi Kawakami3,
＆Motoyuki Itoh1,2
1)Nagoya Univ. Grad. Sch. Sci. ,Div. Biol. Soi. ,
2)Nagoya Univ. IAR, 3NIG.
In
the
spinal
cord,
V2-interneuron
(V2-IN)
progenitors
develop
into
excitatory
V2a-IN
and
inhibitory
V2b-IN.
Previous
studies
have
shown
that
Notch
signaling
is
involved
in
the
maintenance
of
V2-IN
progenitors
(p2)
and
the
V2a/V2b
cell
fate
determination.
Notch
signaling
pathway
can
be
activated
by
different
Notch
ligands
including
Delta
family
proteins.
Delta
proteins
require
Mib -mediated
ubiquitination
for
the
effective
signal
sending
to
Notch.
In
zebrafish
mib
mutants,
p2
was
decreased
and
V2a-IN
was
increased
at
the
expense
of
the
V2b-IN,
suggesting
Mib-mediated
ligand
activation
is
involved
in
both
p2
maintenance
and
V2
cell-fate
choice.
However,
it
remains
unclear
which
Notch
receptors
and
ligands
play
roles
in
two
functions.
To
understand
the
roles
of
the
Notch
receptors
and
ligands
in
the
V2
development,
we
knocked
down
the
expression
of
Notch
and
ligands
by
morpholinos
and
used
their
mutants
in
zebrafish.
We
found
that
p2
was
decreased
in
deltaA;deltaD
double
mutants
and
notch1a-knockdown
embryos.
In
contrast,
loss
of
DeltaA
and
DeltaD
did
not
dramatically
affect
the
V2a/V2b
cell
fate,
whereas
notch1a
knockdown
resulted
in
an
increase
in
V2a-IN
at
the
expense
of
V2b-IN.
These
results
suggest
that
DeltaA
and
DeltaD
play
a
role
cooperatively
in
the
maintenance
of
V2-IN
progenitors
thorough
activation
of
Notch1a.
On
the
other
hand,
Notch1a
activation
is
involved
in
V2a/V2b
cell
fate
determination,
but
its
activation
by
DeltaA
and
DeltaD
is
not
required
or
sufficient
for
the
fate
decision.
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