Biology Reference
In-Depth Information
cog-1
, and another zinc-finger transcription factor,
die-1
, form a bistable
feedback loop that can exist in either one of two states: a high
lsy-6
and
die-1
state that results in the expression of an ASEL-specific gene battery and a
high
cog-1
state that causes the ASE neuron to adopt an ASER fate
(
Johnston
et al
., 2005
).
Studies in
Drosophila
have also provided an interesting case:
mir-279
was
identified in a screen because its loss resulted in ectopic CO
2
-sensing
neurons in the maxillary palps (MPs) in addition to the CO
2
-sensing
neurons normally present in the antenna of the fly (
Cayirlioglu
et al
.,
2008
). These ectopic sensory neurons in the MP were hybrids, with proper-
ties of both CO
2
-sensing neurons and one of two specific subclasses of
olfactory neurons. One of the targets of
mir-279
involved in this process is a
transcription factor called Nerfin-1; however, ectopic expression of Nerfin-
1 by itself is not sufficient to generate CO
2
-sensing neurons, suggesting the
involvement of additional targets. Interestingly, discovery of this role for
mir-279
may have uncovered an evolutionary path in which introduction of
a miRNA was involved. In the fly, CO
2
causes an aversive response;
however, in blood-feeding insects, CO
2
is attractive and it is sensed by
neurons in the MP. It is interesting to speculate that the
mir-279
-mutant
phenotype may have uncovered an intermediate hybrid state on which
selective pressure could have acted to generate the diversity observed
nowadays.
In the chick spinal cord, mir-9 has been implicated in the specification of
different motor neuron subtypes (
Otaegi
et al
., 2011
). mir-9 is transiently
expressed in motor neurons of the lateral motor column (LMC), and its
overexpression causes a change in identity of these neurons to that of the
median motor column. This effect seems to be caused by the mir-9-
mediated repression of
FoxP1
. Interestingly, mir-9 and
FoxP1
are coex-
pressed in LMC motor neurons where mir-9 has been proposed to tune
FoxP1 levels. This is consistent with different
FoxP1
dose requirements
to generate different motor neuron classes (
Dasen
et al
., 2008
;
Rousso
et al
., 2008
).
Another miRNA involved in neuronal differentiation is mir-133. In
human and mouse midbrains, mir-133 seems to negatively regulate dopa-
minergic neuron differentiation through the repression of
Pitx3
,a
bicoid
-
related transcription factor well known to promote dopaminergic neuron
differentiation and survival. In turn, Pitx3 can transcriptionally activate
mir-133 (
Kim
et al
., 2007
). Why would mir-133 be expressed and repress
a prodopaminergic factor in cells that have to become dopaminergic neu-
rons? While the answer is still unclear, one clue may come from an analysis
of
Pitx3
levels in different dopaminergic neuron populations in the brain.
This study showed that
Pitx3
level is about six times higher in dopaminergic
neurons from the ventral tegmental area than in neurons from the substantia
nigra (
Korotkova
et al
., 2005
). It will be interesting to know whether