Biology Reference
In-Depth Information
Other miRNAs seem to distinguish different neuronal—and glial—types
during development, as discussed throughout this chapter. For example,
mir-9 distinguishes cells outside the zebrafish MHB from the progenitors in
the actual MHB; mir-17-3p is important to robustly diversify two pools of
progenitors in the mouse spinal cord, and the presence of
mir-279
allows for
the generation of distinct classes of sensory neurons in
Drosophila.
Notably, miRNAs may also play a role in maintaining the identity of
distinct neuronal classes postdevelopmentally. mir-16 seems to be present at
higher levels in noradrenergic than in serotoninergic neurons, and it is able
to repress serotonin-metabolic enzymes in noradrenergic neurons (
Baudry
et al
., 2010
). Both
in vivo
and
in vitro
—in a bipotent neuroectodermal cell
line that can differentiate into either serotoninergic or noradrenergic neu-
rons—mir-16 inhibits the expression of the serotonin transporter (directly)
as well as of tryptophan hydroxylase (likely indirectly). Loss of mir-16 in
noradrenergic neurons gives them the ability to synthesize, store, and
degrade serotonin without affecting the noradrenaline metabolism. These
findings suggest that miRNAs are likely involved in maintaining well-
defined neuronal classes.
Overall, it seems likely that miRNAs with their versatile repressive
abilities have been able, during evolution, to segregate functions contained
in common precursors into distinct neuronal subpopulations. Further studies
analyzing this role of miRNAs as diversifiers, to generate the vast neuronal
complexity, are necessary and will undoubtedly prove extremely interesting.
4. Integration of miRNA Function into
Gene Regulatory Networks
4.1. Switches or modulators with a few or “hundreds”
of targets?
To fully understand the contribution of miRNA regulation to a biological
phenomenon, it is important to answer questions such as does a given
miRNA act by regulating one or a few major targets, or is it really able to
target dozens or hundreds of them, as prediction algorithms and genome-
wide transcriptome and proteome analyses propose? And, do miRNAs act
as molecular switches, turning off the expression of their targets, or do they
modulate their expression to lower but still detectable levels? These ques-
tions have been raised in multiple occasions since the birth of the field, and
while here we discuss them briefly, for further reading we suggest, among
others,
Flynt and Lai (2008)
.
The proposal that a miRNA can target numerous mRNAs is based on
bioinformatic studies that use combinations of RNA sequence, secondary
structure, and conservation information. These predict that each miRNA
