Biology Reference
In-Depth Information
there is a decrease of proliferation of progenitors in the pallium although
it is unclear whether this is due to direct action of mir-9 on these
progenitors or a consequence of its earlier effect. This decrease in later
progenitor proliferation could be related to the decrease in proliferation of
hNPCs described above. It is interesting to note that in the mouse and
zebrafish, olfactory epithelia miRNAs of the mir-200 family also seem to
regulate neurogenesis at least in part through their action on
Foxg1
(
Choi
et al
., 2008
)
.
In addition to the targets mentioned so far, mir-9 and mir-9* (a miRNA
partially complementary to mir-9 derived from the opposite strand of
the same precursor hairpin) have been shown to repress the well-known,
antineuronal transcriptional repressor, REST/NRSF (RE1 silencing tran-
scription factor/neuron restrictive silencer factor) and its cofactor, CoREST
(
Conaco
et al
., 2006
;
Packer
et al
., 2008
). While these studies were
conducted in cell lines and their contribution
in vivo
should be further
explored, this result is consistent with the proneural role of mir-9 and its
coordinated function with mir-124 to promote neurogenesis as discussed
below.
mir-9
has also been shown to have a role in a well-characterized model
for neurogenesis,
Drosophila
sensory organ development (
Li
et al
., 2006
).
However, in this case, despite
mir-9
being highly conserved, its role seems
to be different than that in vertebrate systems. First,
mir-9
expression in the
nervous systems is not as prominent as in other organisms.
mir-9
is present in
embryonic epithelial cells and in the larval wing disc, but not in the sensory
organ precursors (SOPs) each of which will give rise to a neuron. In fact,
ectopic
mir-9
expression causes a reduction in the number of SOPs
mediated by repression of
Senseless
, a known proneural gene. As expected,
loss of
mir-9
results in additional SOPs, suggesting that
mir-9
in
Drosophila
suppresses neuronal precursor specification in “nonneuronal” tissues.
Another miRNA in
Drosophila
,
mir-7
, complements the function of
mir-9
.
While
mir-9
is expressed in the non-SOP cells,
mir-7
is present in the SOP
where it promotes expression of proneural genes such as
Atonal
and
Senseless
through its negative effect on
E(spl)
(
Li
et al
., 2009
)
.
Interestingly,
mir-7
is
also part of a complex gene regulatory network—involving different players
and a different target—that controls photoreceptor determination (
Li and
Carthew, 2005
).
In mice, mir-124 is expressed somewhat later than mir-9 during devel-
opment, but it is also expressed in neuronal progenitors and mature neurons
as it continues to be expressed into adulthood and is the most abundant
miRNA in the adult mammalian brain (
Deo
et al
., 2006
;
Lagos-Quintana
et al
., 2002
). mir-124 also seems to both repress the expression of neural
progenitor genes as well as induce the expression of neuronal genes to
promote neuronal differentiation (
Coolen and Bally-Cuif, 2009
;
Vo
et al
.,
2010
). These roles of mir-124 are carried out through a number of targets.
