Biology Reference
In-Depth Information
mir-133 is equally present in these two areas and is perhaps involved in
creating this difference, and how this difference may impinge on the
function and susceptibility to degenerate of these two classes of dopaminer-
gic neurons. Alternatively, mir-133 could be part of dynamic regulatory
interactions required for the progression of differentiation from progenitors
to mature dopaminergic neurons.
Such a role for a miRNA has been proposed for mir-96 in controlling
the progression of differentiation in cochlear hair cells in mice. In this case,
loss of mir-96 function (through a point mutation in its seed region) puts a
brake in the differentiation program that leaves both inner and outer hair
cells with an immature morphology, electrophysiology, and innervation
pattern (
Kuhn
et al
., 2011
). Therefore, mir-96 could be in charge of down-
regulating genes required for initial specification but that could later impair
the acquisition of the fully differentiated fate. Identifying the targets of
mir-96 will be essential to pinning down its function.
2.1.4. Maturation
During neuronal maturation, the appropriate connections between neurons
and their targets are established. In addition, in vertebrates, those neurons
that fail to integrate into the corresponding circuits die through apoptosis,
while those that form appropriate connections must inhibit apoptosis since
they have to survive throughout the lifetime of the organism. miRNAs play
roles in these processes as well.
A number of groups have reported roles for miRNAs in regulating
dendritic spine development and plasticity. mir-132 is induced by synaptic
activity and has been shown to increase dendritic length, branching, and
spine density in
in vitro
models using primary cortical and hippocampal
neurons from embryonic or newborn rats (
Vo
et al
., 2005
). In addition,
the expression of mir-132 in the developing rat hippocampus correlates
with a period of active synaptogenesis (
Impey
et al
., 2010
). The effect of
mir-132 to promote spine formation seems to be mediated by p250GAP, a
Rho-family GTPase that regulates actin dynamics (
Vo
et al
., 2005
;
Wayman
et al
., 2008
). More recently, the effect of mir-132 was confirmed
in vivo
in
an adult neurogenesis model: knockout of mir-132 in newborn hippocam-
pal neurons in adult mice decreased dendritic length and arborization
(
Magill
et al
., 2010
). mir-132 has also been implicated in regulating synaptic
maturation during the neonatal period through its action on MeCP2 (
Klein
et al
., 2007
). The interaction with MeCP2 results in a complex regulatory
network that will be further discussed in
Section 3.2
.
The structure and function of synapses can also be regulated by mir-
125b. Overexpression of this miRNA in cultured hippocampal neurons
from rat embryos induced the formation of long and narrow spines with low
mEPSC amplitude (
Edbauer
et al
., 2010
). This morphology correlates with
the timing of mir-125b expression; endogenous levels are high in younger
