Biology Reference
In-Depth Information
new muscle fibers. During this process, satellite cells display two hallmarks
of stem cells: they generate differentiated muscle cells and reconstitute the
satellite cell population through self-renewal. Two related transcription
factors, Pax3 and Pax7, are satellite cell markers and required for the
maintenance of embryonic myoblast populations, suggesting that they
may also be required for adult satellite cell maintenance (
Buckingham,
2006
). Recently, Pax3 and Pax7 have been identified as the targets of a
series of miRNAs, including
miR-1
/
206
,
miR-27,
and
miR-486
(
Chen
et al
., 2010
;
Crist
et al
., 2009
;
Dey
et al
., 2011
;
Hirai
et al
., 2010
). Since
these miRNAs are robustly induced during myogenesis, they may silence
Pax3 and Pax7 to repress stem cell identity in differentiating daughter cells.
Indeed, a role for miRNAs in satellite cell survival and terminal differentia-
tion is supported by the consequence of Dicer depletion in satellite cells
purified from adult mouse muscles (
Chen
et al
., 2010
), which display
increased apoptosis and defective myogenesis upon differentiation induc-
tion. The identification of the specific miRNAs involved as well as their
relevant targets will be of great interest.
5. Concluding Remarks
miRNAs collectively display a number of features indicating that they
are important for muscle biology: some are located within the introns of
dedicated muscle genes like
a
-MHC and
b
-MHC (
van Rooij
et al
., 2007,
2009
), others are under the direct control of myogenic and cardiogenic
transcription factors like MyoD, SRF, and MEF2 (
Liu
et al
., 2007
;
Xin
et al
.,
2009
;
Zhao
et al
., 2005
), and many are expressed specifically and at very
high level throughout the lifetime of muscle cells from birth in the meso-
derm of the zygote to death in the aging adult (
Rao
et al
., 2009
;
Tang
et al
.,
2007
). Unlike myogenic transcription factors, however, muscle miRNAs
are not absolutely required for the specification or differentiation of muscle
cells during development: partially or completely functional muscle systems
form in mutant animals that are depleted of specific muscle miRNAs,
including
miR-1
(
Simon
et al
., 2008
;
Sokol and Ambros, 2005
;
Zhao
et al
., 2007
),
miR-17-92
(
Ventura
et al
., 2008
),
miR-133a-1
/
miR-133a-
2
(
Liu
et al
., 2008
),
miR-143
/
miR-145
(
Boettger
et al
., 2009
;
Elia
et al
.,
2009
;
Xin
et al
., 2009
),
miR-206
(
Williams
et al
., 2009
),
miR-208a
(
Callis
et al
., 2009
;
van Rooij
et al
., 2007
), and
miR-208b
/
miR-499
(
van Rooij
et al
., 2009
). Many of
these mutants die either during embryogenesis or soon
thereafter, however, displaying significant defects in muscle tissue morphol-
ogy and/or size. These phenotypes, along with data that miRNAs like
miR-1
,
miR-133
,
miR-143,
and
miR-145
predominantly regulate the
expression of cytoskeletal components (
Mishima
et al
., 2009
;
Xin
et al
.,
