Biology Reference
In-Depth Information
Abstract
Exquisite regulation of Hox protein activity is fundamental to the regionalization
of the early embryo across diverse taxa. Highlighting the critical importance of
these transcription factors, an astonishing number of different mechanisms
have evolved to tightly coordinate their activity both in time and in space. The
recent identification of numerous microRNAs that are not only embedded within
Hox clusters but also target numerous Hox genes suggests an important role for
these regulatory molecules in shaping Hox protein output. Here, we discuss the
positioning of these miRNAs within clusters over evolutionary time, the unex-
pected complexity in miRNA processing and target interactions, and the current
understanding of Hox-embedded miRNA function during development.
1. Introduction
Hox genes have fascinated developmental biologists for decades given
their central role in regionalization of the early embryo, as demonstrated by the
striking developmental defects observed following their functional alteration.
Since their discovery in
Drosophila
(
Lewis 1963, 1978
), Hox genes have been
identified in all bilaterian lineages and unique Hox signatures in divergent
species likely represent a fundamental mechanism underlying morphological
diversity. Hox genes provide cells their context within the embryonic
anterior-posterior (A-P) axis, allowing them to coordinate within their local
environment to perform specialized functions and give rise to region-specific
morphologies, for example, the choice between vertebrae that are ribless
(cervical) and ribbed (thoracic) in vertebrates, or between a wing and haltere
in
Drosophila
. A unique feature of Hox biology is that multiple genes are
expressed andwork as a coordinated unit, a feature facilitated by their genomic
positioning and by themultilayered and precise control this positioning affords.
In most bilaterian genomes, Hox genes are clustered in an ordered
chromosomal arrangement that is translated into ordered expression along
the embryonic A-P axis, a property termed colinearity. Colinearity is
usually both spatial and temporal. Genes at the 3
0
ends of clusters are
expressed earlier and more anteriorly in the body, and those at the 5
0
ends
are expressed later and more posteriorly, producing a staggered and over-
lapping pattern of expression. It is thought that Hox proteins act combina-
torially, with a given “code” of protein expression specifying each unique
segmental identity. However, in vertebrates, members of paralogous groups
are often redundant and may sometimes provide quantitative rather than
qualitative patterning information. Further, activity is not purely combina-
torial, since the most 5
0
Hox protein(s) expressed in a given segment gener-
ally make the greatest contribution to phenotype, a phenomenon known as
posterior prevalence (
Kessel and Gruss, 1991
;
Kmita and Duboule, 2003
).
