scholarly journals Dorsoventral dissociation of Hox gene expression underpins the diversification of molluscs

2019 ◽  
Author(s):  
Pin Huan ◽  
Qian Wang ◽  
Sujian Tan ◽  
Baozhong Liu

AbstractUnlike the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns and, with some exceptions, have generally been described as lacking the canonical staggered pattern along the anterior-posterior (AP) axis. This difference is unexpected given that almost all molluscs share highly conserved early development. Here, we show that molluscan Hox expression can undergo dynamic changes, which may explain why previous research observed different expression patterns. Moreover, we reveal that a key character of molluscan Hox expression is that the dorsal and ventral expression is dissociated. We then deduce a generalized molluscan Hox expression model, including conserved staggered Hox expression in the neuroectoderm on the ventral side and lineage-specific dorsal expression that strongly correlates with shell formation. This generalized model clarifies a long-standing debate over whether molluscs possess staggered Hox expression and it can be used to explain the diversification of molluscs. In this scenario, the dorsoventral dissociation of Hox expression allows lineage-specific dorsal and ventral patterning in different clades, which may have permitted the evolution of diverse body plans in different molluscan clades.

2019 ◽  
Vol 117 (1) ◽  
pp. 503-512 ◽  
Author(s):  
Pin Huan ◽  
Qian Wang ◽  
Sujian Tan ◽  
Baozhong Liu

In contrast to the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns with differences reported among lineages. Here, we investigate 2 phylogenetically distant molluscs, a gastropod and a polyplacophoran, and show that the Hox expression in both species can be divided into 2 categories. The Hox expression in the ventral ectoderm generally shows a canonical staggered pattern comparable to the patterns of other bilaterians and likely contributes to ventral patterning, such as neurogenesis. The other category of Hox expression on the dorsal side is strongly correlated with shell formation and exhibits lineage-specific characteristics in each class of mollusc. This generalized model of decoupled dorsoventral Hox expression is compatible with known Hox expression data from other molluscan lineages and may represent a key characteristic of molluscan Hox expression. These results support the concept of widespread staggered Hox expression in Mollusca and reveal aspects that may be related to the evolutionary diversification of molluscs. We propose that dorsoventral decoupling of Hox expression allowed lineage-specific dorsal and ventral patterning, which may have facilitated the evolution of diverse body plans in different molluscan lineages.


Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1449-1466 ◽  
Author(s):  
C.E. Nelson ◽  
B.A. Morgan ◽  
A.C. Burke ◽  
E. Laufer ◽  
E. DiMambro ◽  
...  

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3′ genes are expressed in the fore limb bud while the 5′ genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.


Development ◽  
2002 ◽  
Vol 129 (5) ◽  
pp. 1225-1238 ◽  
Author(s):  
Cynthia L. Hughes ◽  
Thomas C. Kaufman

The diversity of the arthropod body plan has long been a fascinating subject of study. A flurry of recent research has analyzed Hox gene expression in various arthropod groups, with hopes of gaining insight into the mechanisms that underlie their evolution. The Hox genes have been analyzed in insects, crustaceans and chelicerates. However, the expression patterns of the Hox genes have not yet been comprehensively analyzed in a myriapod. We present the expression patterns of the ten Hox genes in a centipede, Lithobius atkinsoni, and compare our results to those from studies in other arthropods. We have three major findings. First, we find that Hox gene expression is remarkably dynamic across the arthropods. The expression patterns of the Hox genes in the centipede are in many cases intermediate between those of the chelicerates and those of the insects and crustaceans, consistent with the proposed intermediate phylogenetic position of the Myriapoda. Second, we found two ‘extra’ Hox genes in the centipede compared with those in Drosophila. Based on its pattern of expression, Hox3 appears to have a typical Hox-like role in the centipede, suggesting that the novel functions of the Hox3 homologs zen and bicoid were adopted somewhere in the crustacean-insect clade. In the centipede, the expression of the gene fushi tarazu suggests that it has both a Hox-like role (as in the mite), as well as a role in segmentation (as in insects). This suggests that this dramatic change in function was achieved via a multifunctional intermediate, a condition maintained in the centipede. Last, we found that Hox expression correlates with tagmatic boundaries, consistent with the theory that changes in Hox genes had a major role in evolution of the arthropod body plan.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1288-1288
Author(s):  
Julia Starkova ◽  
Blanka Vicenova ◽  
Roman Krejci ◽  
Harry A. Drabkin ◽  
Jan Trka

Abstract Abstract 1288 Poster Board I-310 Homeodomain (HOX) genes encode transcription factors important for embryonic development. They are involved in normal hemopoiesis regulation and likely also in leukemogenesis as a result of translocations and other aberrations present in leukemias. In previous work Drabkin et al. demonstrated that HOX gene expression patterns differentiate major cytogenetic groups in acute myeloid leukemias. In this study we focused on HOX gene expression in pediatric acute lymphoblastic leukemias (ALL). We were interested if certain HOX genes or expression pattern could distinguish subpopulations of ALL. We analyzed the expression pattern of 21 HOX genes from HOXA and HOXB clusters and non-cluster HOX genes, CDX1 and CDX2 using qRT-PCR approach. We looked at 54 patients chosen according to phenotypic (T-ALL, BCP-ALL), prognostic (PGR – prednisone good responders, PPR – prednisone poor responders) and genotypic (BCR/ABL, MLL/AF4, TEL/AML1, hyperdiploid) characteristics. Overall analysis comparing all studied groups showed that HOXA7 (Kruskal-Wallis test p=0.000045), HOXA3 (p=0.000098), HOXB3 (p=0.00015), HOXA4 (p=0.000619) and HOXB4 (p=0.001925) genes were differently expressed among groups. Wilcoxon signed-rank test, a non-parametric statistical analysis comparing two groups against each other, showed that HOXA3, A4 and B3 distinguish BCP-ALL (w/o fusion gene) and T-ALL. Interestingly, particular HOX genes expression showed significant difference among the groups: HOXA7 gene is significantly downregulated in hyperdiploid ALL (p=0.03) compared to all other subgroups. Furthermore, HOXB7 gene is specifically upregulated in TEL/AML-positive patients (p=0.0048 vs BCP-ALL w/o fusion gene) and CDX2 is downregulated in BCR/ABL-positive patients (p=0.001 vs hyperdiploid; p=0.006 vs TEL/AML1; p=0.03 vs MLL/AF4). Suprisingly, TEL/AML1-positive patients have similar expression of HOXA1-A4 as T-ALL patients. HOX genes expression pattern seemed to differ in MLL/AF4-positive patients according to the age at diagnosis. Three patients younger than 2 months at presentation clustered together in clear contrast to the MLL/AF4-positive patient diagnosed at the age of 13 years with secALL who presented with very low overall expression of all HOX genes. Next, we looked for diversity and similarity between groups. We determined how many HOX genes were expressed differently (p<0.05) and similarly (p=1.0) between particular ALL subtypes. The most outlying couples were T-ALL vs PPR (11 genes differently expressed), T-ALL vs PGR (9 genes) and T-ALL vs TEL/AML1 (6 genes). In contrast, the closest groups were BCR/ABL vs PPR, MLL/AF4 vs T-ALL and MLL/AF4 vs PPR. Our data demonstrate that BCP-ALL (w/o known fusion gene) can be distinguished from T-ALL by the HOX gene expression (in particular HOXA3, HOXB3, HOXA4). Like in AML, expression pattern differs also among the major cytogenetical subgroups of ALL. On the other hand, within the BCP-ALL subgroup, no expression difference was found between patients with good (PGR) and poor (PPR) response to the initial steroid therapy which is known to be an excellent predictor of outcome. HOX genes of interest emerged from our analysis: low expression of HOXA7 in hyperdiploid ALL, highly expressed HOXB7 in TEL/AML1-positive ALL and specifically downregulated CDX2 in BCR/ABL-positive ALL. Age-related differences in expression in MLL/AF4-positive ALL seem to link the expression pattern rather with the relative maturity of the cell undergoing (pre)malignant transformation than with the specific changes caused by the leukemogenesis itself. This hypothesis must be tested in comparison to the HOX genes expression in sorted subtypes of normal T and B precursors. This work was supported by MSM0021620813, IGA NR/9526 and GACR 301/08/P532. Disclosures No relevant conflicts of interest to declare.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1572
Author(s):  
Orit Adato ◽  
Yaron Orenstein ◽  
Juri Kopolovic ◽  
Tamar Juven-Gershon ◽  
Ron Unger

Transcription factors encoded by Homeobox (HOX) genes play numerous key functions during early embryonic development and differentiation. Multiple reports have shown that mis-regulation of HOX gene expression plays key roles in the development of cancers. Their expression levels in cancers tend to differ based on tissue and tumor type. Here, we performed a comprehensive analysis comparing HOX gene expression in different cancer types, obtained from The Cancer Genome Atlas (TCGA), with matched healthy tissues, obtained from Genotype-Tissue Expression (GTEx). We identified and quantified differential expression patterns that confirmed previously identified expression changes and highlighted new differential expression signatures. We discovered differential expression patterns that are in line with patient survival data. This comprehensive and quantitative analysis provides a global picture of HOX genes’ differential expression patterns in different cancer types.


2018 ◽  
Vol 285 (1888) ◽  
pp. 20181513 ◽  
Author(s):  
Tim Wollesen ◽  
Sonia Victoria Rodríguez Monje ◽  
André Luiz de Oliveira ◽  
Andreas Wanninger

Hox genes are expressed along the anterior–posterior body axis in a colinear fashion in the majority of bilaterians. Contrary to polyplacophorans, a group of aculiferan molluscs with conserved ancestral molluscan features, gastropods and cephalopods deviate from this pattern by expressing Hox genes in distinct morphological structures and not in a staggered fashion. Among conchiferans, scaphopods exhibit many similarities with gastropods, cephalopods and bivalves, however, the molecular developmental underpinnings of these similar traits remain unknown. We investigated Hox gene expression in developmental stages of the scaphopod Antalis entalis to elucidate whether these genes are involved in patterning morphological traits shared by their kin conchiferans. Scaphopod Hox genes are predominantly expressed in the foot and mantle but also in the central nervous system. Surprisingly, the scaphopod mid-stage trochophore exhibits a near-to staggered expression of all nine Hox genes identified. Temporal colinearity was not found and early-stage and late-stage trochophores, as well as postmetamorphic individuals, do not show any apparent traces of staggered expression. In these stages, Hox genes are expressed in distinct morphological structures such as the cerebral and pedal ganglia and in the shell field of early-stage trochophores. Interestingly, a re-evaluation of previously published data on early-stage cephalopod embryos and of the gastropod pre-torsional veliger shows that these developmental stages exhibit traces of staggered Hox expression. Considering our results and all gene expression and genomic data available for molluscs as well as other bilaterians, we suggest a last common molluscan ancestor with colinear Hox expression in predominantly ectodermal tissues along the anterior–posterior axis. Subsequently, certain Hox genes have been co-opted into the patterning process of distinct structures (apical organ or prototroch) in conchiferans.


Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2239-2249 ◽  
Author(s):  
A. Abzhanov ◽  
T.C. Kaufman

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.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4614-4614
Author(s):  
Karolina Kramarzova ◽  
Harry Drabkin ◽  
Jan Zuna ◽  
Zuzana Zemanova ◽  
Jan Stary ◽  
...  

Abstract Abstract 4614 Introduction: The homeodomain genes (HOX genes) encode a family of highly conserved transcription factors that play fundamental roles during embryogenesis. HOX genes are also important regulators in hematopoiesis. In leukemogenesis, dysregulated expression of HOX genes has been found. Despite many correlative studies, the mechanism of establishment of leukemia specific HOX gene expression patterns in hematopoietic cells remains to be elucidated. Histone methylases and demethylases (Trithorax (TrxG), JMJD3 and Polycomb-group (PcG) genes) are chromatin modifiers regulating global gene expression through chromatin remodeling in many biological processes. PcG genes can also interact with DNA methyltransferases and alter their activity. Our previously published data showed that HOX gene expression correlated with the level of DNA methylation. These data together with the stabilizing function of PcG genes on HOX expression in embryogenesis suggest the involvement of histone modifiers in the regulation of hematopoietic HOX gene expression. Methods: To investigate the regulation of HOX expression in leukemogenesis, we determined mRNA levels of the representative groups of HOX genes (HOXA, HOXB, CDX1/2), PcG genes (EZH2, BMI1), MLL and demethylases (JMJD3, UTX) in samples of childhood AML (N=41) and healthy controls (N=5). We also studied the dynamics of HOX genes and chromatin modifiers in preleukemic and diagnostic samples of a patient who underwent secondary leukemia. Quantification of gene expression was performed using qPCR assays as previously described. Results: Expression patterns for the majority of HOX genes differed significantly among morphologically defined subgroups of AML with AML M3 having the lowest expression of all HOX genes. Children with AML M5 expressed HOXA cluster at the highest level, while HOXB genes were highly expressed in M5 and M4 subtype. Subgroups defined according to molecular genetics showed similar results. The presence of PML/RARa fusion gene was associated with very low expression of all HOX genes whereas MLL+ and CBFb/MYH11+ patients expressed higher levels of HOXA genes. We also assessed the prognostic significance of particular HOX genes and found that the HOXA cluster was expressed at very low levels in standard risk cases compared to the high risk group (P<0.0001 for most HOXA genes), which is in concordance with previously published results in adult AML (Andreeff et al. 2008). Determination of mRNA levels of histone modifiers showed an overall level of high expression across various AML subgroups. Nevertheless, some were uniformly expressed in AML patients (EZH2, MLL), while others were differentially expressed with the lowest level in the M3 subtype (BMI1, JMJD3). Interestingly, we found a correlation between HOX gene expression and levels of JMJD3, which was mainly evident in CBFb-MYH11+, PML-RARa+ and AML1-ETO+ patients. JMJD3 levels were also correlated with another demethylase, UTX. A positive trend between HOX gene expression and JMJD3 was identified in healthy controls as well. Analysis of the sample from preleukemic period of the patient with secondary leukemia (secALL with MLL translocation) allowed us to study the dynamics of HOX gene expression during leukemogenesis. The diagnostic secALL sample showed an expression pattern of HOX genes typical for MLL+ leukemia. However, the profile of HOX genes in preleukemic sample (16 months before secALL) resembled the pattern found in healthy controls. Nonetheless, 90% of these seemingly normal hematopoietic cells were confirmed by FISH analysis to carry MLL/FOXO3A. Thus, even though MLL is a well known regulator of HOX genes, there must be an additional mechanism, that establishes the expression pattern of HOX genes typical in MLL+ patients. Conclusion: In summary, we identified different expression patterns of HOX genes in particular subtypes of childhood AML that significantly correlated with prognosis. Our results indicate that histone modifiers JMJD3 and UTX might be involved in the regulation of HOX gene expression. Moreover, these data also suggest that histone demethylases could cooperate with specific genetic aberrations implicated in chromatin remodeling on regulation of HOX genes. The analysis of secondary leukemia suggests that additional alterations are required to deregulate HOX expression in at least some MLL+ patients. Disclosures: No relevant conflicts of interest to declare.


2010 ◽  
Vol 10 ◽  
pp. 2207-2214 ◽  
Author(s):  
A. J. Durston ◽  
H. J. Jansen ◽  
S. A. Wacker

We review a recently discovered developmental mechanism. Anterior-posterior positional information for the vertebrate trunk is generated by sequential interactions between a timer in the early nonorganizer mesoderm (NOM) and the Spemann organizer (SO). The timer is characterized by temporally collinear activation of a series of Hox genes in the early ventral and lateral mesoderm (i.e., the NOM) of the Xenopus gastrula. This early Hox gene expression is transient, unless it is stabilized by signals from the SO. The NOM and the SO undergo timed interactions due to morphogenetic movements during gastrulation, which lead to the formation of an anterior-posterior axial pattern and stable Hox gene expression. When separated from each other, neither the NOM nor the SO is able to induce anterior-posterior pattern formation of the trunk. We present a model describing that the NOM acquires transiently stable hox codes and spatial collinearity, and that morphogenetic movements then continually bring new cells from the NOM within the range of SO signals that cause transfer of the mesodermal pattern to a stable pattern in neurectoderm and, thereby, create patterned axial structures. In doing so, the age of the NOM, but not the age of the SO, defines positional values along the anterior-posterior axis. We postulate that the temporal information from the NOM is linked to mesodermal Hox expression. The role of the SO for trunk patterning turns out to be the induction of neural tissue as prerequisite for neural hox patterning. Apparently, development of a stable anterior-posterior pattern requires neural hox patterning. We believe that this mechanism represents a developmental principle.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David A. Salamanca-Díaz ◽  
Andrew D. Calcino ◽  
André L. de Oliveira ◽  
Andreas Wanninger

AbstractHox genes are key developmental regulators that are involved in establishing morphological features during animal ontogeny. They are commonly expressed along the anterior–posterior axis in a staggered, or collinear, fashion. In mollusks, the repertoire of body plans is widely diverse and current data suggest their involvement during development of landmark morphological traits in Conchifera, one of the two major lineages that comprises those taxa that originated from a uni-shelled ancestor (Monoplacophora, Gastropoda, Cephalopoda, Scaphopoda, Bivalvia). For most clades, and bivalves in particular, data on Hox gene expression throughout ontogeny are scarce. We thus investigated Hox expression during development of the quagga mussel, Dreissena rostriformis, to elucidate to which degree they might contribute to specific phenotypic traits as in other conchiferans. The Hox/ParaHox complement of Mollusca typically comprises 14 genes, 13 of which are present in bivalve genomes including Dreissena. We describe here expression of 9 Hox genes and the ParaHox gene Xlox during Dreissena development. Hox expression in Dreissena is first detected in the gastrula stage with widely overlapping expression domains of most genes. In the trochophore stage, Hox gene expression shifts towards more compact, largely mesodermal domains. Only few of these domains can be assigned to specific developing morphological structures such as Hox1 in the shell field and Xlox in the hindgut. We did not find traces of spatial or temporal staggered expression of Hox genes in Dreissena. Our data support the notion that Hox gene expression has been coopted independently, and to varying degrees, into lineage-specific structures in the respective conchiferan clades. The non-collinear mode of Hox expression in Dreissena might be a result of the low degree of body plan regionalization along the bivalve anterior–posterior axis as exemplified by the lack of key morphological traits such as a distinct head, cephalic tentacles, radula apparatus, and a simplified central nervous system.


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