Biology Reference
In-Depth Information
Table 9.1
MicroRNAs and network motifs: Experimental evidence
System
Factors
Reference
FBLs
Human granulocytes miR-223; NFI-A; CEBP
Fazi
et al
. (2005)
C. elegans
ASE
neurons
lsy-6; miR-273; die-1;
cog-1
Johnston
et al
. (2005)
C. elegans
VPCs
miR-61; lin-12; vav-1
Yoo and Greenwald (2005)
Drosophila
R cells
miR-7; Yan; Pnt-P1
Li and Carthew (2005)
Drosophila
SOPs
miR-9a; Sens; Proneural
Li
et al
. (2006)
Cardiomyocytes
miR-1; miR-133l SRF;
MEF-2
Chen
et al
. (2006)
FFLs
Human B cells
miR-17-5p; c-myc; E2F
O'Donnell
et al
. (2005)
Drosophila
R cells
miR-7; Yan; Pnt-P1
Li
et al
. (2009)
to a high miR-7/low YAN stable state (
Graham
et al
., 2010
). These two
states are stabilized through double-negative FBLs between YAN and its
repressors,and dictate whether a cell remains multipotent or differentiated
(
Graham
et al
., 2010
). EGF receptor signaling induces the phosphorylation
of YAN and a switching from the multipotent to the differentiated state.
Nevertheless, the FBL between YAN and miR-7 is essential neither for
the switch nor for the stable maintenance of the cells' states. Instead, the
role of this FBL is probably to generate robustness to the network. When
development is perturbed in a
miR-7
mutant by oscillating temperature,
the switch occurs less robustly and errors in cell fate are observed (
Li
et al
.,
2009
). These errors are undetectable under uniform temperature condi-
tions. Thus, this FBL can make differentiation robust to environmental
perturbation.
A different mechanism is found in the differentiation of the
Drosophila
sensory organ precursors (SOPs;
Li
et al
., 2006
). In this case, the miRNA is
not itself part of a FBL but rather it regulates the responsiveness of the FBL.
miR-9a
represses expression of
Senseless
, which encodes a TF that induces
SOP differentiation. The SOP cell fate choice is made by coupling Notch
signaling to a positive FBL between various TFs, including Senseless. This
choice does not fundamentally depend on
miR-9a
repression of
Senseless
,as
miR-9a
mutants are still capable of specifying their SOPs. Nevertheless, up
to 40% of mutant animals make extra sensory organs (
Li
et al
., 2006
).
miR-9a
thresholds
Senseless
expression such that, unless a threshold of
Senseless
expression is achieved, the TF FBL is not engaged and SOPs are not
specified (
Cohen
et al
., 2006
). Thus,
miR-9a
buffers SOP differentiation
against fluctuations of Senseless.
