Biology Reference
In-Depth Information
1. INTRODUCTION
The formation of an embryo from a single fertilized cell is one the most
fundamental processes in nature. Adiverse array ofmorphogenetic strategies has
evolved to bring together various differentiated cell types and tissues, whichwill
eventually produce a coherent organism. These strategies generally require, at
some point, the determination of global embryonic axes, such as the anterior to
posterior (AP) axis from the head to the caudal part of the embryo. The sub-
sequent deployment of various structures along this major body axis can be
achieved in different ways, for example, with or without segmentation. Devel-
opment can thus rely exclusively upon cell lineage instructions, like in
Caenorhabditis elegans
, or upon the reiteration of segments that at later stages will
acquire their identities. In the case of segmentation, two programs can be
followed: (1) segmentation can be sequential in time and progress from anterior
to posterior, as in all vertebrates andmany invertebrates or (2) segmentation can
be simultaneous, like in
Drosophila
and other long germ band insects. Impor-
tantly, in all these scenarios, the identification of structures along this AP axis
depends on the activity of the homeobox-containing
Hox
gene family
(
de Rosa et al., 1999; Garcia-Fernandez, 2005; McGinnis & Krumlauf, 1992
).
Various combinations of HOX proteins along the AP axis will trigger the
morphogenesis of different structures, whereas incorrect combinations will ill-
specify body parts, a phenomenon referred to as homeotic transformations
(
Lewis, 1978
). The correct distribution of protein members from the HOX
family to theAP axis is therefore of utmost importance. The precision achieved
in this spatial distribution is largely due to a mechanism that translates the geno-
mic position of any given
Hox
gene into both its order of activation and its
maintained activity (
Figs. 4.1 and 4.2
). This “spatial collinearity”, first recog-
nized by Lewis when working out the genetics of the Bithorax complex
(BC-X) in
Drosophila melanogaster
mutants (
Lewis, 1978
), was observed in ver-
tebrates to regulate this highly conserved
Hox
gene family as well (
Duboule &
Dolle, 1989; Gaunt, Sharpe, & Duboule, 1988; Graham, Papalopulu, &
Krumlauf, 1989; Kmita & Duboule, 2003; Krumlauf, 1994
). In animals that
develop in an anterior to posterior temporal sequence,
Hox
genes are further
activated in a temporal sequence that reflects the genes' positions along the
Hox
clusters, a mechanism referred to as temporal collinearity (
Izpisua-
Belmonte, Falkenstein, Dolle, Renucci, & Duboule, 1991
). Over the years,
this progressive gene activation in time and space, following the genomic
topography, has proved to be a difficult question to solve. However, recent
