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genes that impair differentiation (mostly transcription factors and signaling
pathways) (
Dugas
et al
., 2010
;
Zhao
et al
., 2010
). mir-23 also represses an
OPC-expressed gene, Lamin B1 (
Lmnb1
), that otherwise inhibits the mor-
phological differentiation of OLs (
Lin and Fu, 2009
). Finally, mir-138
specifically promotes the first stage of OL differentiation, acquisition of
the premyelinating OL state, while preventing progression to the later
stage, thus extending the intermediate stage that is necessary to establish
the number of sheaths that a cell will form (
Dugas
et al
., 2010
).
In
C. elegans
, a single miRNA,
mir-228
, has been identified, to date, to
be expressed in sheath and/or socket cells that are glia-like support cells for
the ciliated sensory neurons in the worm (
Pierce
et al
., 2008
). While these
cells do not produce myelin, it will be interesting to see whether
mir-228
plays a role in some step during their differentiation.
2.3. miRNAs have highly context-dependent functions
In addition to the commonalities of miRNA functions in diverse systems, it
has also become evident that even the most conserved miRNAs can play
substantially different roles in different organisms. Even in the same organ-
ism, the same miRNA can have distinct roles in different cell types or at
different time points in development. This observation that miRNAs can
have distinct context-dependent functions has been explored by
Gao
(2010)
, and we will expand it here with more recent examples from the
literature.
First, even highly conserved miRNAs can have diverse roles in different
organisms. For example, as we have seen above, mir-9 promotes neurogen-
esis in multiple vertebrate systems (
Bonev
et al
., 2011
;
Conaco
et al
., 2006
;
Lagos-Quintana
et al
., 2002
;
Leucht
et al
., 2008
;
Packer
et al
., 2008
;
Wienholds
et al
., 2005
;
Zhao
et al
., 2009
). However, in
Drosophila
, it acts
in nonneural cells to repress neuronal differentiation (
Li
et al
., 2006
).
Another case of seemingly distinct functions in different organisms is
provided by mir-124. While in vertebrate systems it seems to promote
neurogenesis in multiple types of neuronal precursors, in
Aplysia
and in
C. elegans
, mir-124 is only expressed in sensory neurons, and at least in
Aplysia
, while it is not yet known whether it plays a role in neurogenesis, it
has been shown to be involved in synaptic plasticity (
Rajasethupathy
et al
.,
2009
). In
C. elegans
, its precise function is still unknown, but in its absence,
the neurons where it is expressed are still present, arguing against a strong
role in neurogenesis (
Clark
et al
., 2010
).
The second level at which the same miRNA can display segregation of
function is at the tissue level within the same organism. A number of
miRNAs fit this category, with distinct targets and thus different effects in
different tissues. mir-138 was presented above as an important player in OL
differentiation; however, it has also been implicated in spine morphogenesis
