scholarly journals Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position

2018 ◽  
Author(s):  
Chloe Moreau ◽  
Paolo Caldarelli ◽  
Didier Rocancourt ◽  
Julian Roussel ◽  
Nicolas Denans ◽  
...  
Keyword(s):  
Natural Variation ◽  
Molecular Mechanisms ◽  
Hox Genes ◽  
Gene Activation ◽  
The Body ◽  
Three Dimensions ◽  
Limb Patterning ◽  
Hox Gene ◽  
Limb Position ◽  
Control Limb

SummaryLimb position along the body is highly consistent within one species but very variable among vertebrates. Despite major advances in our understanding of limb patterning in three dimensions, how limbs reproducibly form along the anteroposterior axis remains largely unknown. Hox genes have long been suspected to control limb position, however supporting evidences are mostly correlative and their role in this process remains unclear. Here we show that Hox genes determine the avian forelimb position in a two-step process: first, their sequential collinear activation during gastrulation controls the relative position of their own successive expression domains along the body axis. Then, within these collinear domains, Hox genes differentially activate or repress the genetic cascade responsible for forelimb initiation. Furthermore, we provide evidences that changes in the timing of collinear Hox gene activation might underlie natural variation in forelimb position between different birds. Altogether our results which characterize the cellular and molecular mechanisms underlying the regulation and natural variation of forelimb position in avians, show a direct and early role for Hox genes in this process.

Homeobox genes and models for patterning the hindbrain and branchial arches

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 187-196 ◽  
Author(s):  
Paul Hunt ◽  
Jenny Whiting ◽  
Ian Muchamore ◽  
Heather Marshall ◽  
Robb Krumlauf
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Expression Pattern ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Neural Plate ◽  
The Body ◽  
Hox Gene ◽  
Hox Code ◽  
Branchial Region

Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton. Recently it has been proposed that the rhombomererestricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate. We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuroepithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest's rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations. The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region. Our data are consistent with the idea that the branchial region of the head arose in evolution before the more anterior parts, the development of the branchial region employing the Hox genes in a more determinate patterning system. In this scenario, the anterior parts of the head arose subsequently, which may explain the greater importance of interactions in their development, and the fact that Antennapedia class Hox genes are not expressed there.

Hox genes and the evolution of diverse body plans

1995 ◽  
Vol 349 (1329) ◽  
pp. 313-319 ◽  
Keyword(s):  
Transcription Factors ◽  
Hox Genes ◽  
Body Plan ◽  
The Body ◽  
Chromosomal Organization ◽  
Hox Gene ◽  
Body Regions ◽  
Taxonomic Groups ◽  
Novel Model ◽  
Sequence Characteristics

Homeobox genes encode transcription factors that carry out diverse roles during development. They are widely distributed among eukaryotes, but appear to have undergone an extensive radiation in the earliest metazoa, to generate a range of homeobox subclasses now shared between diverse metazoan phyla. The Hox genes comprise one of these subfamilies, defined as much by conserved chromosomal organization and expression as by sequence characteristics. These Hox genes act as markers of position along the antero—posterior axis of the body in nematodes, arthropods, chordates, and by implication, most other triploblastic phyla. In the arthropods this role is visualized most clearly in the control of segment identity. Exactly how Hox genes control the structure of segments is not yet understood, but their differential deployment between segments provides a model for the basis of segment diversity. Within the arthropods, distantly related taxonomic groups with very different body plans (insects, crustaceans) may share the same set of Hox genes. The expression of these Hox genes provides a new character to define the homology of different body regions. Comparisons of Hox gene deployment between insects and a branchiopod crustacean suggest a novel model for the derivation of the insect body plan.

Crustacean (malacostracan) Hox genes and the evolution of the arthropod trunk

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2239-2249 ◽  
Author(s):  
A. Abzhanov ◽  
T.C. Kaufman
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
The Body ◽  
Ancestral State ◽  
Porcellio Scaber ◽  
Hox Gene ◽  
Overlapping Domains ◽  
Discrete Domains

Representatives of the Insecta and the Malacostraca (higher crustaceans) have highly derived body plans subdivided into several tagma, groups of segments united by a common function and/or morphology. The tagmatization of segments in the trunk, the part of the body between head and telson, in both lineages is thought to have evolved independently from ancestors with a distinct head but a homonomous, undifferentiated trunk. In the branchiopod crustacean, Artemia franciscana, the trunk Hox genes are expressed in broad overlapping domains suggesting a conserved ancestral state (Averof, M. and Akam, M. (1995) Nature 376, 420–423). In comparison, in insects, the Antennapedia-class genes of the homeotic clusters are more regionally deployed into distinct domains where they serve to control the morphology of the different trunk segments. Thus an originally Artemia-like pattern of homeotic gene expression has apparently been modified in the insect lineage associated with and perhaps facilitating the observed pattern of tagmatization. Since insects are the only arthropods with a derived trunk tagmosis tested to date, we examined the expression patterns of the Hox genes Antp, Ubx and abd-A in the malacostracan crustacean Porcellio scaber (Oniscidae, Isopoda). We found that, unlike the pattern seen in Artemia, these genes are expressed in well-defined discrete domains coinciding with tagmatic boundaries which are distinct from those of the insects. Our observations suggest that, during the independent tagmatization in insects and malacostracan crustaceans, the homologous ‘trunk’ genes evolved to perform different developmental functions. We also propose that, in each lineage, the changes in Hox gene expression pattern may have been important in trunk tagmatization.

A C. elegans Hox gene switches on, off, on and off again to regulate proliferation, differentiation and morphogenesis

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1651-1661 ◽  
Author(s):  
S.J. Salser ◽  
C. Kenyon
Keyword(s):  
Cellular Response ◽  
Hox Genes ◽  
Sense Organ ◽  
Cellular Level ◽  
The Body ◽  
Body Region ◽  
Hox Gene ◽  
C Elegans ◽  
Independent Events ◽  
Gene Switches

Hox genes establish body pattern throughout the animal kingdom, but the role these genes play at the cellular level to modify and shape parts of the body remains a mystery. We find that the C. elegans Antennapedia homolog, mab-5, sequentially programs many independent events within individual cell lineages. In one body region, mab-5 first switches ON in a lineage to stimulate proliferation, then OFF to specify epidermal structures, then ON in just one branch of the lineage to promote neuroblast formation, and finally OFF to permit proper sense organ morphology. In a neighboring lineage, continuous mab-5 expression leads to a different pattern of development. Thus, this Hox gene achieves much of its power to diversify the anteroposterior axis through fine spatiotemporal differences in expression coupled with a changing pattern of cellular response.

scholarly journals Paralogous HOX13 Genes in Human Cancers

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 699 ◽  
Author(s):  
Gerardo Botti ◽  
Clemente Cillo ◽  
Rossella De Cecio ◽  
Maria Gabriella Malzone ◽  
Monica Cantile
Keyword(s):  
Hox Genes ◽  
Integration Site ◽  
Gene Activation ◽  
Tumor Development ◽  
Group 13 ◽  
Developmental Abnormalities ◽  
Hox Gene ◽  
Body Regions ◽  
Relevant Role ◽  
Spatio Temporal

Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.

scholarly journals Chromatin-bound CRM1 recruits SET-Nup214 and NPM1c onto HOX clusters causing aberrant HOX expression in leukemia cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Masahiro Oka ◽  
Sonoko Mura ◽  
Mayumi Otani ◽  
Yoichi Miyamoto ◽  
Jumpei Nogami ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Hox Genes ◽  
Gene Activation ◽  
Nuclear Export Signal ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Hox Gene ◽  
Hox Cluster

We previously demonstrated that CRM1, a major nuclear export factor, accumulates at Hox cluster regions to recruit nucleoporin-fusion protein Nup98HoxA9, resulting in robust activation of Hox genes (Oka et al., 2016). However, whether this phenomenon is general to other leukemogenic proteins remains unknown. Here, we show that two other leukemogenic proteins, nucleoporin-fusion SET-Nup214 and the NPM1 mutant, NPM1c, which contains a nuclear export signal (NES) at its C-terminus and is one of the most frequent mutations in acute myeloid leukemia, are recruited to the HOX cluster region via chromatin-bound CRM1, leading to HOX gene activation in human leukemia cells. Furthermore, we demonstrate that this mechanism is highly sensitive to a CRM1 inhibitor in leukemia cell line. Together, these findings indicate that CRM1 acts as a key molecule that connects leukemogenic proteins to aberrant HOX gene regulation either via nucleoporin-CRM1 interaction (for SET-Nup214) or NES-CRM1 interaction (for NPM1c).

scholarly journals Anterior Hox Genes and the Process of Cephalization

2021 ◽  
Vol 9 ◽  
Author(s):  
James C.-G. Hombría ◽  
Mar García-Ferrés ◽  
Carlos Sánchez-Higueras
Keyword(s):  
Nervous Tissue ◽  
Hox Genes ◽  
The Body ◽  
Sensory Organs ◽  
Hox Gene ◽  
Anterior Segments

During evolution, bilateral animals have experienced a progressive process of cephalization with the anterior concentration of nervous tissue, sensory organs and the appearance of dedicated feeding structures surrounding the mouth. Cephalization has been achieved by the specialization of the unsegmented anterior end of the body (the acron) and the sequential recruitment to the head of adjacent anterior segments. Here we review the key developmental contribution of Hox1–5 genes to the formation of cephalic structures in vertebrates and arthropods and discuss how this evolved. The appearance of Hox cephalic genes preceded the evolution of a highly specialized head in both groups, indicating that Hox gene involvement in the control of cephalic structures was acquired independently during the evolution of vertebrates and invertebrates to regulate the genes required for head innovation.

scholarly journals Transcriptional Regulation and Implications for Controlling Hox Gene Expression

2022 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Zainab Afzal ◽  
Robb Krumlauf
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
Hox Genes ◽  
Regional Identity ◽  
Regulatory Mechanisms ◽  
Regulation Of Transcription ◽  
Axial Patterning ◽  
Hox Gene ◽  
Molecular Framework ◽  
Combinatorial Code

Hox genes play key roles in axial patterning and regulating the regional identity of cells and tissues in a wide variety of animals from invertebrates to vertebrates. Nested domains of Hox expression generate a combinatorial code that provides a molecular framework for specifying the properties of tissues along the A–P axis. Hence, it is important to understand the regulatory mechanisms that coordinately control the precise patterns of the transcription of clustered Hox genes required for their roles in development. New insights are emerging about the dynamics and molecular mechanisms governing transcriptional regulation, and there is interest in understanding how these may play a role in contributing to the regulation of the expression of the clustered Hox genes. In this review, we summarize some of the recent findings, ideas and emerging mechanisms underlying the regulation of transcription in general and consider how they may be relevant to understanding the transcriptional regulation of Hox genes.

scholarly journals The unusual gene order in the Echinoderm Hox cluster is related to the embryo and larva symmetries

2015 ◽  
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Sea Urchin ◽  
Gene Sequence ◽  
Hox Genes ◽  
Developmental Stages ◽  
Rotational Symmetry ◽  
The Body ◽  
Gene Location ◽  
Linear Arrangement ◽  
Hox Gene ◽  
Hox Cluster

Background: Hox gene collinearity relates the sequential location of Hox genes in the 3´ to 5´ direction on the chromosome with the linear arrangement of the body elements along the anterior-posterior (A/P) axis of bilaterian embryos. This spatial Hox gene collinearity has been almost universally respected in diverse organisms like worms, insects or vertebrates. It is therefore surprising that the above well established collinearity rule is violated in the case of Echinoderms. No explanation of this violation is apparent. Here a hypothesis is put forward which provides a cue to understand the abnormal serial gene location in the sea urchin disorganized Hox cluster. Results: Bilateral symmetry along the A/P embryo axis is established at the very early stages of ontogeny of the sea urchin. For the subsequent developmental stages, rotational symmetry emerges in the vestibula larva. In analogy to the linear A/P case, the circular topology of modules might be a reflection of the architectural restructuring of the Hox loci where the 3´ and 5´ ends of the Hox cluster approach each other so that a closed contour of the chromatin fiber is formed. At a later stage, the break and opening of the cluster contour at the level of Hox4 combined with the rotational symmetry leads to the observed Hox gene sequence that violates the standard 3´ to 5´ collinearity. Conclusion: The unusual gene series manifests the congruence of Hox gene sequence in the cluster with the circular arrangement of the sea urchin primary podia. Accordingly, the Hox sequence after the break at Hox4 is not a violation but an extension of Hox gene collinearity to animals with rotational symmetry.

scholarly journals Lin28a/let-7 pathway modulates the Hox code via Polycomb regulation during axial patterning in vertebrates

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tempei Sato ◽  
Kensuke Kataoka ◽  
Yoshiaki Ito ◽  
Shigetoshi Yokoyama ◽  
Masafumi Inui ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hox Genes ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
The Body ◽  
Tight Control ◽  
Tail Bud ◽  
Axial Patterning ◽  
Spatiotemporal Expression ◽  
Hox Code

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a–/– mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a–/– mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the ‘Hox code’ via Polycomb regulation during axial patterning.

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