scholarly journals Homeotic Genes: Clustering, Modularity, and Diversity

2021 ◽  
Vol 9 ◽  
Author(s):  
Nikhil Hajirnis ◽  
Rakesh K. Mishra
Keyword(s):  
Genome Engineering ◽  
Hox Genes ◽  
Hair Follicles ◽  
Axis Formation ◽  
Homeotic Genes ◽  
Holistic View ◽  
Evolutionarily Conserved ◽  
Genome Assemblies ◽  
Anterior Posterior

Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of Hox to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of Hox in various organisms. Further, we revisit their discovery and regulation in Drosophila melanogaster. We also review their regulation in different arthropods and vertebrates, with a significant focus on Hox expression in the crustacean Parahyale hawaiensis. It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of Hox in the animal world.

Hox genes and the evolution of vertebrate axial morphology

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 333-346 ◽  
Author(s):  
A.C. Burke ◽  
C.E. Nelson ◽  
B.A. Morgan ◽  
C. Tabin
Keyword(s):  
Hox Genes ◽  
Cervical Vertebrae ◽  
Homeobox Gene ◽  
Paraxial Mesoderm ◽  
Thoracic Vertebrae ◽  
Homeotic Genes ◽  
Evolutionary Variation ◽  
Axial Morphology ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

A common form of evolutionary variation between vertebrate taxa is the different numbers of segments that contribute to various regions of the anterior-posterior axis; cervical vertebrae, thoracic vertebrae, etc. The term ‘transposition’ is used to describe this phenomenon. Genetic experiments with homeotic genes in mice have demonstrated that Hox genes are in part responsible for the specification of segmental identity along the anterior-posterior axis, and it has been proposed that an axial Hox code determines the morphology of individual vertebrae (Kessel, M. and Gruss, P. (1990) Science 249, 347–379). This paper presents a comparative study of the developmental patterns of homeobox gene expression and developmental morphology between animals that have homologous regulatory genes but different morphologies. The axial expression boundaries of 23 Hox genes were examined in the paraxial mesoderm of chick, and 16 in mouse embryos by in situ hybridization and immunolocalization techniques. Hox gene anterior expression boundaries were found to be transposed in concert with morphological boundaries. This data contributes a mechanistic level to the assumed homology of these regions in vertebrates. The recognition of mechanistic homology supports the historical homology of basic patterning mechanisms between all organisms that share these genes.

scholarly journals Roles of Drosophila Hox Genes in the Assembly of Neuromuscular Networks and Behavior

2022 ◽  
Vol 9 ◽  
Author(s):  
Rohit Joshi ◽  
Rashmi Sipani ◽  
Asif Bakshi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Motor Neuron ◽  
Hox Genes ◽  
Neural Circuitry ◽  
Neuron Morphology ◽  
Developing Region ◽  
And Behavior ◽  
Anterior Posterior

Hox genes have been known for specifying the anterior-posterior axis (AP) in bilaterian body plans. Studies in vertebrates have shown their importance in developing region-specific neural circuitry and diversifying motor neuron pools. In Drosophila, they are instrumental for segment-specific neurogenesis and myogenesis early in development. Their robust expression in differentiated neurons implied their role in assembling region-specific neuromuscular networks. In the last decade, studies in Drosophila have unequivocally established that Hox genes go beyond their conventional functions of generating cellular diversity along the AP axis of the developing central nervous system. These roles range from establishing and maintaining the neuromuscular networks to controlling their function by regulating the motor neuron morphology and neurophysiology, thereby directly impacting the behavior. Here we summarize the limited knowledge on the role of Drosophila Hox genes in the assembly of region-specific neuromuscular networks and their effect on associated behavior.

scholarly journals Wnt/β-catenin signaling is an evolutionarily conserved determinant of chordate dorsal organizer

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Iryna Kozmikova ◽  
Zbynek Kozmik
Keyword(s):  
Cell Fate ◽  
Current View ◽  
Specific Gene ◽  
Axis Formation ◽  
Dependent Manner ◽  
Evolutionarily Conserved ◽  
Dorsal Axis ◽  
Dorsal Cells ◽  
Dorsal Cell Fate

Deciphering the mechanisms of axis formation in amphioxus is a key step to understanding the evolution of chordate body plan. The current view is that Nodal signaling is the only factor promoting the dorsal axis specification in the amphioxus, whereas Wnt/β-catenin signaling plays no role in this process. Here, we re-examined the role of Wnt/βcatenin signaling in the dorsal/ventral patterning of amphioxus embryo. We demonstrated that the spatial activity of Wnt/β-catenin signaling is located in presumptive dorsal cells from cleavage to gastrula stage, and provided functional evidence that Wnt/β-catenin signaling is necessary for the specification of dorsal cell fate in a stage-dependent manner. Microinjection of Wnt8 and Wnt11 mRNA induced ectopic dorsal axis in neurulae and larvae. Finally, we demonstrated that Nodal and Wnt/β-catenin signaling cooperate to promote the dorsal-specific gene expression in amphioxus gastrula. Our study reveals high evolutionary conservation of dorsal organizer formation in the chordate lineage.

Oocyte determination and the origin of polarity in Drosophila: the role of the spindle genes

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4927-4937 ◽  
Author(s):  
A. Gonzalez-Reyes ◽  
H. Elliott ◽  
D. St Johnston
Keyword(s):  
Symmetry Breaking ◽  
Germinal Vesicle ◽  
Follicle Cells ◽  
Axis Formation ◽  
Main Body ◽  
Nurse Cells ◽  
Egg Chambers ◽  
Anterior Posterior ◽  
Oocyte Selection

The two main body axes in Drosophila become polarised as a result of a series of symmetry-breaking steps during oogenesis. Two of the sixteen germline cells in each egg chamber develop as pro-oocytes, and the first asymmetry arises when one of these cells is selected to become the oocyte. Anterior-posterior polarity originates when the oocyte then comes to lie posterior to the nurse cells and signals through the Gurken/Egfr pathway to induce the adjacent follicle cells to adopt a posterior fate. This directs the movement of the germinal vesicle and associated gurken mRNA from the posterior to an anterior corner of the oocyte, where Gurken protein signals for a second time to induce the dorsal follicle cells, thereby polarising the dorsal-ventral axis. Here we describe a group of five genes, the spindle loci, which are required for each of these polarising events. spindle mutants inhibit the induction of both the posterior and dorsal follicle cells by disrupting the localisation and translation of gurken mRNA. Moreover, the oocyte often fails to reach the posterior of mutant egg chambers and differentiates abnormally. Finally, double mutants cause both pro-oocytes to develop as oocytes, by delaying the choice between these two cells. Thus, these mutants reveal a novel link between oocyte selection, oocyte positioning and axis formation in Drosophila, leading us to propose that the spindle genes act in a process that is common to several of these events.

scholarly journals The role of Pten in anterior–posterior (AP) axis formation in the mouse embryo

2008 ◽  
Vol 319 (2) ◽  
pp. 584
Author(s):  
Joshua E. Bloomekatz ◽  
Andrew Rakeman ◽  
Heather Alcorn ◽  
Kathryn V. Anderson
Keyword(s):  
Mouse Embryo ◽  
Axis Formation ◽  
Anterior Posterior

scholarly journals Time-Space Translation: A Developmental Principle

2010 ◽  
Vol 10 ◽  
pp. 2207-2214 ◽  
Author(s):  
A. J. Durston ◽  
H. J. Jansen ◽  
S. A. Wacker
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Positional Information ◽  
Hox Gene ◽  
Morphogenetic Movements ◽  
Spemann Organizer ◽  
Stable Pattern ◽  
Time Space ◽  
Anterior Posterior

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.

scholarly journals DrosophilaHox genes induce melanised pseudo-tumours when misexpressed in hemocytes

2018 ◽  
Author(s):  
Titus Ponrathnam ◽  
Rakesh K Mishra
Keyword(s):  
Blood Cell ◽  
Blood Cells ◽  
Hox Genes ◽  
Pupal Stage ◽  
Cell Number ◽  
Homeotic Genes ◽  
Cell Identity ◽  
Proliferation And Differentiation ◽  
Anterior Posterior ◽  
Acute Myeloid

AbstractHomeotic genes are the key early determinants of cell identity along the anterior-posterior body axis across bilaterians. More recently, however, several late non-homeotic functions of hox genes have emerged in a variety of organogenesis processes, including in mammals. Being crucial factors in determining cell identity and organogenesis, the misregulation of hox genes is likely to be associated with defects in these processes. Several studies have reported misexpression of hox genes in a variety of malignancies including acute myeloid leukaemia. Considering thatDrosophilais a well-established model for the study of haematopoiesis, we ectopically expressed the hox genes,Dfd,Ubx,abd-AandAbd-B, to ask if and how it will alter the process of haematopoiesis. We observed black melanised spots circulating in the viscera of the larvae and extensive lethality at during the pupal stage in these conditions. Such abnormalities are the hallmark of dysregulated haematopoiesis. We also observed an increase in blood cell number as well as their enhanced differentiation into lamellocytes. Our study opens a new possibility of addressing the function hox genes in normal and leukemogenic hematopoiesis with potential implications in downstream targets for diagnostic markers and therapy.SummaryDrosophilaHox genes, when expressed in blood cells, are leukemogenic, induce cell autonomous proliferation and differentiation. This reinforces previous studies in vertebrates and allows for Hox induced leukaemia to be studied inDrosophila.

The evolving role of Hox genes in arthropods

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 209-215
Author(s):  
Michael Akam ◽  
Michalis Averof ◽  
James Castelli-Gair ◽  
Rachel Dawes ◽  
Francesco Falciani ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Early Development ◽  
Hox Genes ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Gene Duplications ◽  
Fushi Tarazu ◽  
Hox Gene ◽  
Hox Cluster

Comparisons between Hox genes in different arthropods suggest that the diversity of Antennapedia-class homeotic genes present in modern insects had already arisen before the divergence of insects and crustaceans, probably during the Cambrian. Hox gene duplications are therefore unlikely to have occurred concomitantly with trunk segment diversification in the lineage leading to insects. Available data suggest that domains of homeotic gene expression are also generally conserved among insects, but changes in Hox gene regulation may have played a significant role in segment diversification. Differences that have been documented alter specific aspects of Hox gene regulation within segments and correlate with alterations in segment morphology rather than overt homeotic transformations. The Drosophila Hox cluster contains several homeobox genes that are not homeotic genes – bicoid, fushi-tarazu and zen. The role of these genes during early development has been studied in some detail. It appears to be without parallel among the vertebrate Hox genes. No well conserved homologues of these genes have been found in other taxa, suggesting that they are evolving faster than the homeotic genes. Relatively divergent Antp-class genes isolated from other insects are probably homologues of fushi-tarazu, but these are almost unrecognisable outside of their homeodomains, and have accumulated approximately 10 times as many changes in their homeodomains as have homeotic genes in the same comparisons. They show conserved patterns of expression in the nervous system, but not during early development.

scholarly journals Lessons on gene regulation learnt from the Drosophila melanogaster bithorax complex

2020 ◽  
Vol 64 (1-2-3) ◽  
pp. 151-158
Author(s):  
Arumugam Srinivasan ◽  
Rakesh K. Mishra
Keyword(s):  
Hox Genes ◽  
Regulatory Elements ◽  
The Body ◽  
Body Axis ◽  
Chromatin Domain ◽  
Homeotic Genes ◽  
Regulatory Processes ◽  
Entire Complex ◽  
Cis And Trans ◽  
Anterior Posterior

Homeotic or Hox genes determine the anterior-posterior body axis in all bilaterians. As expected, Hox genes are highly conserved across bilaterians. Interestingly, however, the peculiar organization of Hox genes in the form of clusters where the order of occurrence of genes in the genome corresponds to the order in which they regulate segmental identity of anterior-posterior body axis is also conserved. The relation between collinearity of arrangement of genes on the chromosomes and spatial function along the body axis has attracted attention to exploring its relevance in the precise regulation of Hox genes. Conservation of genes and their arrangement suggests a linkage between co-regulation and the higher order chromatin organization of the entire complex. To this end, we and others have used Drosophila as the model system to understand the cis-and trans-regulatory components of Hox genes. A number of chromatin-level regulatory elements, like chromatin domain boundaries, and Polycomb Response Elements (PREs) have been discovered in this process. Interestingly, much of what has emerged from the study of homeotic genes, the cis-elements and protein factors, have relevance across the genome in a large number of regulatory events beyond the Hox genes. Here, we review our findings and discuss their genome-wide implications in complex regulatory processes.

Patterning of the embryo along the anterior-posterior axis: the role of the caudal genes

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3805-3814 ◽  
Author(s):  
M. Epstein ◽  
G. Pillemer ◽  
R. Yelin ◽  
J.K. Yisraeli ◽  
A. Fainsod
Keyword(s):  
Antisense Rna ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Regulatory Function ◽  
Regulatory Interactions ◽  
C Elegans ◽  
Posterior Position ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

Patterning along the anterior-posterior axis takes place during gastrulation and early neurulation. Homeobox genes like Otx-2 and members of the Hox family have been implicated in this process. The caudal genes in Drosophila and C. elegans have been shown to determine posterior fates. In vertebrates, the caudal genes begin their expression during gastrulation and they take up a posterior position. By injecting sense and antisense RNA of the Xenopus caudal gene Xcad-2, we have studied a number of regulatory interactions among homeobox genes along the anterior-posterior axis. Initially, the Xcad-2 and Otx-2 genes are mutually repressed and, by late gastrulation, they mark the posterior- or anterior-most domains of the embryo, respectively. During late gastrulation and neurulation, Xcad-2 plays an additional regulatory function in relation to the Hox genes. Hox genes normally expressed anteriorly are repressed by Xcad-2 overexpression while those normally expressed posteriorly exhibit more anterior expression. The results show that the caudal genes are part of a posterior determining network which during early gastrulation functions in the subdivision of the embryo into anterior head and trunk domains. Later in gastrulation and neurulation these genes play a role in the patterning of the trunk region.

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