Biology Reference
In-Depth Information
3.2.4. miR-208/-499 mutants in cardiac muscle
As mentioned above,
miR-208a
,
miR-208b,
and
miR-499
are encoded in
the introns of three myosin genes:
myh6
,
myh7
, and
myh7b,
respectively.
Evidence in adults that these miRNAs function to control the expression
levels of each other's host gene (
Callis
et al
., 2009
;
van Rooij
et al
., 2007,
2009
) suggested that they may also orchestrate the developmental transition
from fetal cardiac
b
-MHC expression to adult cardiac
a
-MHC expression.
miR-208a
mutants as well as
miR-208b
/
miR-499
double mutants proceed
through development normally, however, indicating that the function of
these miRNAs to modulate the
a
-MHC/
b
-MHC ratio is limited to the
adult (
Callis
et al
., 2009
;
van Rooij
et al
., 2007, 2009
). These
miR-208b
/
miR-499
double mutants display a substantial loss of type I myofibers in the
soleus, indicating a redundant function for these two miRNAs in skeletal
muscle (
van Rooij
et al
., 2009
).
3.2.5. miR-17-92 in the heart
Recent analysis of a mouse mutant for the
miR-17-92
polycistronic cluster,
which encodes members of the
miR-17
,
-18
,
-19
,
-20,
and -
92
families,
indicates that these miRNAs play a role in heart development (
Ventura
et al
., 2008
;
Wang
et al
., 2010
). Despite the low expression of these
miRNAs in the heart,
miR-17-92
mutant embryos are perinatal lethal and
display strong ventricular septal and outflow tract defects in which the aorta
rises from the right ventricle instead of the left ventricle (
Ventura
et al
.,
2008
;
Wang
et al
., 2010
). This morphological defect correlates with an
increase in Islet1-positive cardiac progenitor cells during heart formation
(
Wang
et al
., 2010
), suggesting that
miR-17-92
miRNAs are involved in the
differentiation of the outflow tract myocardium. Evidence that the
miR-17-
92
locus is a direct target of the bone morphogenetic protein (BMP)
signaling pathway and genetically interacts with
bmp4
locus during outflow
tract formation (
Wang
et al
., 2010
) suggests that BMP signaling regulates
miR-17-92
to promote myocardial differentiation.
4. miRNAs in Muscle Stem Cells
miRNAs are known to play important roles in regulating stem cell
self-renewal and differentiation in a variety of tissues (
Gangaraju and Lin,
2009
), and a series of papers have addressed whether muscle miRNAs may
be involved in controlling satellite cell behavior (
Chen
et al
., 2010
;
Crist
et al
., 2009
;
Hirai
et al
., 2010
). Satellite cells are small, mononucleate cells
that reside under the basal lamina of vertebrate muscle fibers. They are
quiescent under normal physiological conditions, but in response to envi-
ronmental factors can restore damaged muscle fibers or form completely