Biology Reference
In-Depth Information
Target Hox genes
miRNA
“Tuning”
“Failsafe”
Figure 2.2
Potential functional interactions between Hox-embedded miRNAs
(yellow) and their Hox targets (blue) along the anterior-posterior embryonic axis,
based on anticipated extent of coexpression. Where coexpressed, the miRNA could
modulate and optimize target output. The positioning of these miRNAs more 5
0
in the
cluster suggests their expression will extend more posteriorly and act as a failsafe
mechanism to prevent output of aberrant transcripts.
miRNA-target interactions are clearly predicted around targets' posterior
boundaries, but they could be important in any region sensitive to target
dosage. Vertebrate homeotic transformations often cluster at morphological
transitions (e.g., cervical-thoracic, or thoracic-lumbar) (
Wellik, 2009
), sug-
gesting heightened sensitivity to Hox dosage at these locations (although this
may also to some degree reflect the relative easewithwhich transformations are
identified). It is therefore, interesting to note a correlation between miRNA
positions, their targets, and major morphological transition points. For exam-
ple,
miR-196
forms a posterior bracket for genes involved in thoracic/trunk
morphology. mir-196 is predicted or known to target 75% of the
Hox6-
8
genes in mammals, which collectively specify thoracic identities and whose
dosages are apparently most critical at each end of the thoracic region
(
McIntyre
et al
., 2007
;
van den Akker
et al
., 2001
).
miR-196
negatively
regulates
Hoxb-8
both anterior and posterior to the thoracic region (
Asli and
Kessel, 2010
;
Hornstein
et al
., 2005
;
McGlinn
et al
., 2009
) and knockdown
perturbs vertebral identities at the cervical-thoracic transition (
McGlinn
et al
.,
2009
;see
Section 6.3
). Thus, at least for this target, miRNA regulation occurs
in both anterior and posterior regions of its expression.
Finally, it is interesting to note that although
miR-196
targets are
genomically located more 3
0
, they rarely overlap with vertebrate
miR-10
targets suggesting clear division of function. However, this division is less
clear in
Drosophila
, where
miR-10
and
miR-iab-4/8
share three predicted
target genes.
In the following sections, we examine the developmental expression of
Hox-embedded miRNAs in the context of their predicted Hox targets and
review studies testing these interactions and their functional importance
in vivo
.
