Biology Reference
In-Depth Information
While the
miR-57
enhancer is positively regulated by the Abd-class
Nob
-
1,
miR-57
, in turn, directly targets
nob-1
. High-resolution expression
analysis and lineage mapping revealed that the two genes are coexpressed in
all
nob-1-
expressing cells; however,
nob-1
expression precedes
miR-57
by
approximately one cell division. This interaction suggests that
miR-57
may
act as part of a switch mechanism required to inactivate
nob-1
during lineage
progression. Genetic data strongly support a functional interaction
in vivo.
miR-57
loss-of-function partially rescues defects associated with a
nob-1
hypomorphic allele. Further,
miR-57
misexpression phenocopies posterior
patterning defects found in
nob-1
null embryos.
miR-57
null animals show
temperature-sensitive sterility and partially penetrant embryonic or larval
arrest with defects in tail morphology. Whether or which of these pheno-
types are due to
nob-1
misregulation is unknown but confirms a clear, if
partially redundant, patterning role for
miR-57
(
Zhao
et al
., 2010
)
.
4.2.3. Vertebrate
mir-10
In many vertebrate species,
miR-10
paralogs are expressed early in develop-
ment with an anterior limit roughly at the level of
Hox4
paralogs (
Darnell
et al
., 2006
;
He
et al
., 2011a
;
Kloosterman
et al
., 2006
;
Mansfield
et al
., 2004
;
Wienholds
et al
., 2005
;
Woltering and Durston, 2006, 2008
). In zebrafish,
expression is observed in the posterior trunk region at early stages, including
both paraxial mesoderm and the central nervous system (CNS) tissue, with
expression becoming largely restricted to the CNS over time (
Kloosterman
et al
., 2006
;
Wienholds
et al
., 2005
;
Woltering and Durston, 2008
).
miR-10
paralogs exhibit differential anterior boundaries of expression within the
CNS;
miR-10a
and
miR-10c
are caudal to rhombomere 6/7, while
miR-10b
and
miR-10d
are caudal to the hindbrain. It is quite striking that
miR-10d
expression is so similar to paralogs, given that all Hox genes surrounding
miR-10d
and global regulatory elements of this cluster were lost (
Woltering
and Durston, 2006
). In chick, additional expression was observed in the
developing branchial arches and forelimb bud, though absent from the
hindlimb (
Darnell
et al
., 2006
). High-throughput direct sequencing of
miRNAs expressed in whole mouse embryos at E7.5, E9.5, and E12.5 has
allowed the first glimpse of relative expression levels of Hox-embedded
paralogous miRNAs during development (
Chiang
et al
., 2010
). Absolute
read counts for
miR-10a
and
miR-10b
are broadly comparable; however, the
relative temporal expression of each miRNA is different.
miR-10b
is highest
at E7.5, while
miR-10a
exhibited highest relative expression at E12.5. Deep
sequencing approaches also indicate expression of
miR-10
paralogs in
developing somites (
Rathjen
et al
., 2009
) as well as the embryonic and
In vivo
validation of
miR-10
targeting has been most extensively char-
acterized in zebrafish. Two predicted targets,
HoxB1a
and
HoxB3a
, are
expressed in discrete rhombomeric stripes, with additional diffuse
