Biology Reference
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well as in the more complex vertebrate systems. Studies in this wide range of
model organisms have been extremely fruitful as they have uncovered
common themes in the roles of miRNAs in the nervous system and will
likely help us understand their functions from an evolutionary perspective.
The first miRNAs shown to have a role in development of the correct
architecture of the vertebrate nervous system were those of the mir-430
family in zebrafish (
Giraldez
et al
., 2005
). Fish embryos lacking Dicer
showed severe brain morphogenesis defects which could be rescued by
injection of preprocessed mir-430 miRNAs. This pioneering study
prompted numerous others that have identified other miRNAs and their
targets that act at these early stages of neural development.
While a lot of the earlier evidence for involvement of miRNAs in all
steps of vertebrate neural development was obtained from Dicer knockout
experiments, results from Dicer knockouts should be interpreted carefully as
Dicer is known to be involved in the processing of other essential noncod-
ing RNAs (rRNAs, snoRNAs, tRNAs) (
Cole
et al
., 2009
;
Ender
et al
.,
2008
;
Liang and Crooke, 2011
;
Saraiya and Wang, 2008
). Thus, we have
chosen to focus here on some of the cases of nervous system development
where specific miRNAs have been implicated.
2. Diverse Roles of miRNAs in Nervous
System Development and Function
2.1. miRNAs act at all steps of neuronal development
2.1.1. Patterning
Patterning of the developing vertebrate neuroectoderm that gives rise to all
different mature structures of the nervous system is a complex process that
relies on multiple secreted signals emanating from specific regions. Combi-
nations of these signals result in regional domains with particular patterns of
transcription factor expression that will give rise to different neuronal and
glial pools. A number of miRNAs have been implicated in refining the
boundaries of these domains, perhaps fulfilling a role that is best suited for
this kind of repressor. A few of these are presented below.
Patterning of the midbrain and anterior hindbrain has long been known
to be controlled by an organizing center located at their boundary
(the midbrain-hindbrain boundary or MHB), primarily through Wnt and
Fgf signaling (
Wurst and Bally-Cuif, 2001
). Bally-Cuif and colleagues have
shown that in zebrafish, mir-9 is involved in maintaining the MHB limits
during development. mir-9 is expressed extensively within the neural tube
except in the MHB (
Leucht
et al
., 2008
). Ectopic expression of mir-9 causes
a loss of this organizing center due to ectopic repression of genes required
for MHB function. In contrast, loss of mir-9 causes an expansion of the
