Current Topics in Developmental Biology Volume 88, 2009, Pages 35-61 Hox Genes

Le volume entier est dédié aux gènes Hox, édité par Olivier Pourquié, qui en a écrit la préface (et contribue au chapitre 7, voir ci-dessous).

Attention, les doi ne sont pas encore fonctionnels, pour une liste des papiers suivez le lien donné par Tom : http://www.sciencedirect.com/science/bookseries/00702153

Chapter 2 Evolution of the Hox Gene Complex from an Evolutionary Ground State

Walter J. Gehring, Urs Kloter and Hiroshi Suga

doi:10.1016/S0070-2153(09)88002-2

In this chapter, we consider the question of how the ordered clusters of Hox genes arose during evolution. Since ordered Hox clusters are found in all major superphyla, we have to assume that the Hox clusters arose before the Cambrian “explosion” giving rise to all of these taxa. Based on his studies of the bithorax complex (BX-C) in Drosophila Lewis considered the ground state to be the mesothoracic segment (T2) since the deletion of all of the genes of the BX-C leads to a transformation of all segments from T3 to A8/9 (the last abdominal segment) into T2 segments. We define the developmental ground state genetically, by assuming that loss-of-function mutants lead to transformations toward the ground state, whereas gain-of-function mutants lead to homeotic transformations away from the ground state. By this definition, T2 also represents the developmental ground state, if one includes the anterior genes, that is, those of the Antennapedia complex. We have reconstructed the evolution of the Hox cluster on the basis of known genetic mechanisms which involve unequal crossover and lead from an urhox gene, first to an anterior and a posterior gene and subsequently to intermediate genes which are progressively inserted, between the anterior and posterior genes. These intermediate genes are recombinant due to unequal crossover, whereas the anterior and posterior genes are not affected and therefore had the longest time to diverge from the urhox gene. The molecular phylogenetic analysis strongly supports this model. We consider the ground state to be both developmental and evolutionary and to represent the prototypic body segment. It corresponds to T2 and is specified by Antennapedia or Hox6, respectively. Experiments in the mouse also suggest that the ground state is a thoracic segment. Evolution leads from the prototypic segment to segmental divergence in both the anterior and posterior direction. The most anterior head and tail segments are specified by homeobox genes localized outside of the cluster.

Chapter 7 Establishment of Hox Vertebral Identities in the Embryonic Spine Precursors

Tadahiro Iimura, Nicolas Denans and Olivier Pourquié

doi:10.1016/S0070-2153(09)88007-1

The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements—the vertebrae—along the anteroposterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator—the segmentation clock—which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients—the wavefront—which depends on the Wnt, FGF, and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral, and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes—a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the anteroposterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a crosstalk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development.

Chapter 8 Hox, Cdx, and Anteroposterior Patterning in the Mouse Embryo

Teddy Younga and Jacqueline Deschampsa

doi:10.1016/S0070-2153(09)88008-3

Cdx and Hox gene families descend from the same ProtoHox cluster, already present in the common ancestors of bilaterians and cnidarians, and thought to act by providing anteroposterior (A-P) positional identity to axial tissues in all bilaterians. Mouse Cdx and Hox genes still exhibit common features in their early expression and function. The initiation and early shaping of Hox and Cdx transcriptional domains in mouse embryos are very similar, in keeping with their common involvement in conveying A-P information to the nascent tissues during embryonic axial elongation. Considerations of the impact on axial patterning of the early expression phase of these genes that correlates with the temporally collinear expression of 3′-5′ Hox genes suggest that it is concerned with the acquisition of A-P information by the three germ layers as the axis extends. This early A-P information acquired by all cells emerging from the primitive streak or tailbud and their neighbors in the caudal neural plate gets further modulated by the second phase of gene expression occurring later as the tissues mature and differentiate along the growing axis. We discuss the possibility that regulatory phase 1, common to all Cdx and Hox genes, is inherent to the concerted mechanism sequentially turning on 3′-5′ Hox genes at early stages, and keeping expression of the initiated genes subsequently in the new materials added posteriorly at the axis extends. The posterior Hox gene expression domain would be subsequently complemented by Hox regulatory phase 2, consisting in a variety of gene-specific, region-specific, and/or tissue-specific gene expression controls. We also touch on the unanswered question whether vertebrate Cdx gene expression delivers A-P positional information in its own right, as Caudal does in Drosophila, or whether it does so exclusively by upregulating Hox genes.

Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression

Tadahiro Iimura & Olivier Pourquié

Nature Vol 442, 2006 doi:10.1038/nature04838

The vertebral column exhibits segmentation and regionalization along the antero-posterior axis. During embryogenesis, the rhythmic production of the precursors of the vertebrae, the somites, imposes a segmented aspect to the spine, whereas the spine’s regional differentiation is controlled by Hox genes. Here we show that in the paraxial mesoderm, Hoxb genes are first activated in a temporal collinear fashion in precursors located in the epiblast lateral to the primitive streak. Our data suggest that collinear activation of Hoxb genes regulates the flux of cells from the epiblast to the streak and thus directly controls the establishment of the genes’ characteristic nested expression domains in the somites. This suggests that establishment of the spatial co-linearity in the embryo is directly controlled by the Hox genes themselves.

The rise and fall of Hox gene clusters

Denis Duboule

Development 134, 2549-2560(2007) doi:10.1242/dev.001065

Although all bilaterian animals have a related set of Hox genes, the genomic organization of this gene complement comes in different flavors. In some unrelated species, Hox genes are clustered;in others, they are not. This indicates that the bilaterian ancestor had a clustered Hox gene family and that, subsequently, this genomic organization was either maintained or lost. Remarkably, the tightest organization is found in vertebrates, raising the embarrassingly finalistic possibility that vertebrates have maintained best this ancestral configuration. Alternatively, could they have co-evolved with an increased ‘organization’ of the Hox clusters, possibly linked to their genomic amplification, which would be at odds with our current perception of evolutionary mechanisms? When discussing the why’s and how’s of Hox gene clustering, we need to account for three points: the mechanisms of cluster evolution; the underlying biological constraints; and the developmental modes of the animals under consideration. By integrating these parameters, general conclusions emerge that can help solve the aforementioned dilemma.

The role of Hox genes during vertebrate limb development.

Zakany J, Duboule D.

Curr Opin Genet Dev. 2007 Aug;17(4):359-66 doi:10.1016/j.gde.2007.05.011

Part of: Volume 17, Issue 4, Pages 259-368 (August 2007) Pattern formation and developmental mechanisms
Edited by Ross Cagan and Christine Hartmann

The potential role of Hox genes during vertebrate limb development was brought into focus by gene expression analyses in mice (P Dolle, JC Izpisua-Belmonte, H Falkenstein, A Renucci, D Duboule, Nature 1989, 342:767-772), at a time when limb growth and patterning were thought to depend upon two distinct and rather independent systems of coordinates; one for the anterior-to-posterior axis and the other for the proximal-to-distal axis (see D Duboule, P Dolle, EMBO J 1989, 8:1497-1505). Over the past years, the function and regulation of these genes have been addressed using both gain-of-function and loss-of-function approaches in chick and mice. The use of multiple mutations either in cis-configuration in trans-configuration or in cis/trans configurations, has confirmed that Hox genes are essential for proper limb development, where they participate in both the growth and organization of the structures. Even though their molecular mechanisms of action remain somewhat elusive, the results of these extensive genetic analyses confirm that, during the development of the limbs, the various axes cannot be considered in isolation from each other and that a more holistic view of limb development should prevail over a simple cartesian, chess grid-like approach of these complex structures. With this in mind, the functional input of Hox genes during limb growth and development can now be re-assessed.

Hox Genes and Axial Specification in Vertebrates

Ann Campbell Burke and Julie L. Nowicki

American Zoologist 2001 41(3):687-697; doi:10.1093/icb/41.3.687

INTRODUCTION
Experimental embryology provides a means for exploring the intrinsic mechanisms that underlie morphological evolution. This paper will discuss experimental results that explore the evolutionary significance of Hox gene expression in the patterning of the anterior-posterior (AP) axis in vertebrates. The detailed experiments are reported elsewhere (Nowicki and Burke, 2000). This paper will focus on a discussion of their relevance to understanding the role developmental mechanisms play in generating axial pattern, and how those mechanisms may act as nodal points in the evolution of morphology.

The colinear, anterior to posterior expression domains of the Hox genes in vertebrate embryos is strongly correlated with regional changes in vertebral morphology. The limbs of tetrapods are consistently aligned with specific areas of the vertebral column. However, control of limb development is apparently situated in the lateral plate mesoderm, and has been experimentally shown to be independent of an axial Hox code (Cohn et al., 1997, Nature 387:97–101). We have used experimental manipulation of chick embryos to test the causal role of Hox genes in patterning derivatives of the paraxial mesoderm. Hox expression in heterotopically transplanted segmental plate responds in a manner consistent with a patterning role for these genes in the morphological behavior of the transplants. Expression is maintained in dorsal paraxial regions where patterning is also intrinsic to the donor site of the graft. However, expression is apparently lost in somite cells that migrate into the host lateral plate environment and form appropriate host-level muscles. This arrangement could enable increased plasticity in the evolution of transpositional

Hox genes and morphological identity: axial versus lateral patterning in the vertebrate mesoderm [direct to reprint link]

JL Nowicki and AC Burke

Development, Vol 127, Issue 19 4265-4275

The successful organization of the vertebrate body requires that local information in the embryo be translated into a functional, global pattern. Somite cells form the bulk of the musculoskeletal system. Heterotopic transplants of segmental plate along the axis from quail to chick were performed to test the correlation between autonomous morphological patterning and Hox gene expression in somite subpopulations. The data presented strengthen the correlation of Hox gene expression with axial specification and focus on the significance of Hox genes in specific derivatives of the somites. We have defined two anatomical compartments of the body based on the embryonic origin of the cells making up contributing structures: the dorsal compartment, formed from purely somitic cell populations; and the ventral compartment comprising cells from somites and lateral plate. The boundary between these anatomical compartments is termed the somitic frontier. Somitic tissue transplanted between axial levels retains both original Hox expression and morphological identity in the dorsal compartment. In contrast, migrating lateral somitic cells crossing the somitic frontier do not maintain donor Hox expression but apparently adopt the Hox expression of the lateral plate and participate in the morphology appropriate to the host level. Dorsal and ventral compartments, as defined here, have relevance for experimental manipulations that influence somite cell behavior. The correlation of Hox expression profiles and patterning behavior of cells in these two compartments supports the hypothesis of independent Hox codes in paraxial and lateral plate mesoderm.

Hox genes specify vertebral types in the presomitic mesoderm
Marta Carapuço, Ana Nóvoa, Nicoletta Bobola, and Moisés Mallo
Genes & Dev. 2005. 19: 2116-2121 doi:10.1101/gad.338705

We show here that expression of Hoxa10 in the presomitic mesoderm is sufficient to confer a Hox group 10 patterning program to the somite, producing vertebrae without ribs, an effect not achieved when Hoxa10 is expressed in the somites. In addition, Hox group 11-dependent vertebral sacralization requires Hoxa11 expression in the presomitic mesoderm, while their caudal differentiation requires that Hoxa11 is expressed in the somites. Therefore, Hox gene patterning activity is different in the somites and presomitic mesoderm, the latter being very prominent for Hox gene-mediated patterning of the axial skeleton. This is further supported by our finding that inactivation of Gbx2, a homeobox-containing gene expressed in the presomitic mesoderm but not in the somites, produced Hox-like phenotypes in the axial skeleton without affecting Hox gene expression.

An autopodial-like pattern of Hox expression in the fins of a basal actinopterygian fish

Davis MC, Dahn RD, Shubin NH.

Nature 447, 473-476 (24 May 2007) | doi:10.1038/nature05838

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Le plan complet existe dans un espace “mathématique” où l’évolution l’a élu en agissant sur un paramètre peut-être unique. Ce faisant, d’un coup d’un seul, les vertébrés sont apparus, avec tous leurs attributs. Ce faisant, d’un coup d’un seul, les vertébrés sont apparus, avec tous leurs attributs.
Via

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Comparative analyses of Hox gene expression and regulation in teleost fish and tetrapods support the long-entrenched notion that the distal region of tetrapod limbs, containing the wrist, ankle and digits, is an evolutionary novelty. Data from fossils support the notion that the unique features of tetrapod limbs were assembled over evolutionary time in the paired fins of fish. The challenge in linking developmental and palaeontological approaches has been that developmental data for fins and limbs compare only highly derived teleosts and tetrapods; what is lacking are data from extant taxa that retain greater portions of the fin skeletal morphology considered primitive to all bony fish. Here, we report on the expression and function of genes implicated in the origin of the autopod in a basal actinopterygian, Polyodon spathula. Polyodon exhibits a late-phase, inverted collinear expression of 5′ HoxD genes, a pattern of expression long considered a developmental hallmark of the autopod and shown in tetrapods to be controlled by a ‘digit enhancer’ region. These data show that aspects of the development of the autopod are primitive to tetrapods and that the origin of digits entailed the redeployment of ancient patterns of gene activity.

Tri-phasic expression of posterior Hox genes during development of pectoral fins in zebrafish: Implications for the evolution of vertebrate paired appendages

Ahn D, Ho RK

Dev Biol (2008 ) Article in press

“D’un coup d’un seul” hein ?

During development of the limbs, Hox genes belonging to the paralogous groups 9–13 are expressed in three distinct phases, which play key roles in the segmental patterning of limb skeletons. In teleost fishes, which have a very different organization in their fin skeletons, it is not clear whether a similar patterning mechanism is at work. To determine whether Hox genes are also expressed in several distinct phases during teleost paired fin development, we re-analyzed the expression patterns of hox9–13 genes during development of pectoral fins in zebrafish. We found that, similar to tetrapod Hox genes, expression of hoxa/d genes in zebrafish pectoral fins occurs in three distinct phases, in which the most distal/third phase is correlated with the development of the most distal structure of the fin, the fin blade. Like in tetrapods, hox gene expression in zebrafish pectoral fins during the distal/third phase is dependent upon sonic hedgehog signaling (hoxa and hoxd genes) and the presence of a long-range enhancer (hoxa genes), which indicates that the regulatory mechanisms underlying tri-phasic expression of Hox genes have remained relatively unchanged during evolution. Our results suggest that, although simpler in organization, teleost fins do have a distal structure that might be considered comparable to the autopod region of limbs.

Regulatory constraints in the evolution of the tetrapod limb anterior–posterior polarity

Basile Tarchini, Denis Duboule and Marie Kmita

Nature 443, 985-988 (26 October 2006) | doi:10.1038/nature05247

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From the conclusion :

Consequently, we suggest that tetrapod limbs evolved along with the recruitment of the Hox collinear mechanism implemented in the developing body axis. This regulatory co-option imposed collinearity within limb buds, leading to the posterior-only expression of 5′-located Hox genes. Because these latter genes have the capacity to elicit Shh transcription, Shh signalling was confined to posterior limb bud cells, and hence the limb emerged with a built-in A–P polarity. Alternatively, all HOX proteins originally may have had the capacity to regulate Shh, this property being subsequently restricted to some genes only, to generate an A–P polarized structure. However, the absence of animals with appendages showing a truly bilateral symmetry, including ancestral tetrapod fossils, makes the latter scenario unlikely.
In the former view, the limb A–P polarity is a collateral effect of the genetic strategy co-opted for the distal extension of our limbs, a process highly constrained by the intrinsic logic of our body architecture. The necessity of restricting expression of 59-located Hox genes caudally during gastrulation to prevent the deleterious effects of their products if expressed too rostrally in the main body axis (for example, see ref. 24), is thus probably the origin of their posterior expression in limb buds and of the consequent appendage A–P polarity. In this context, rather than the result of the selection of an independent regulatory strategy applied to an appendage because of the obvious adaptative advantages associated with such a polarity, we may consider that this polarity simply reflects the most parsimonious way of producing a limb.

Abstract

The anterior to posterior (A–P) polarity of the tetrapod limb is determined by the confined expression of Sonic hedgehog (Shh) at the posterior margin of developing early limb buds, under the control of HOX proteins encoded by gene members of both the HoxA and HoxD clusters. Here, we use a set of partial deletions to show that only the last four Hox paralogy groups can elicit this response: that is, precisely those genes whose expression is excluded from most anterior limb bud cells owing to their collinear transcriptional activation. We propose that the limb A–P polarity is produced as a collateral effect of Hox gene collinearity, a process highly constrained by its crucial importance during trunk development. In this view, the co-option of the trunk collinear mechanism, along with the emergence of limbs, imposed an A–P polarity to these structures as the most parsimonious solution. This in turn further contributed to stabilize the architecture and operational mode of this genetic system.