scholarly journals Disappearance of Temporal Collinearity in Vertebrates and Its Eventual Reappearance

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1018
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Hox Genes ◽  
Mouse Embryos ◽  
Limb Bud ◽  
Biophysical Model ◽  
Embryonic Cells ◽  
Hox Gene ◽  
Mutant Cells ◽  
Hox Clusters ◽  
Chip Chip

In 1999 T. Kondo and D. Duboule performed excisions of posterior upstream DNA domains in mouse embryos and they observed that for an extended excision (including Evx gene) the Hox genes of the cluster were simultaneously expressed with the first Hoxd1 gene ‘as if’ Temporal Collinearity (TC) had disappeared. According to a Biophysical Model (BM) during Hox gene expression, Hox clusters behave similar toexpanding elastic springs. For the extended upstream DNA excision, BM predicts the TC disappearance and an experiment is proposed to test this BM prediction. In the chick limb bud C. Tickle et al. observed that the excision of the apical ectodermal ridge (AER) caused the inhibition of HoxA13 expression. However, the implantation of FGF soaked beads at the tip of the limb could surprisingly rescue HoxA13 expression after 24 hours so that TC is restored.Brachyury transcription factor (TF) is essential in identifying the targets of this transcription and a chromatin immunoprecipitation microarray chip (ChIP-chip) was produced which can be inserted in the mouse embryonic cells. It is here proposed to insert this chip in the mutant cells where TC has disappeared and compare it to the limb bud case.Is TC restored? It is an important issue worth exploring.

scholarly journals Physical Laws shape up HOX Gene Collinearity

2021 ◽  
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Hox Genes ◽  
Biophysical Model ◽  
Mathematical Property ◽  
Hox Gene ◽  
Embryonic Tissues ◽  
Transcription Factory ◽  
Animal Phyla ◽  
Physical Forces ◽  
Physical Laws ◽  
Hox Clusters

Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3’ to 5’ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior – Posterior axis of the embyo. Expression of Hox1 occurs in E1. Hox2 in E2, Hox3 in E3… Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is Hox1 expressed in E1, later is Hox2 expressed in E2, followed by Hox3 in E3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) was formulated and tested during the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. Symmetry is a physical-mathematical property of Matter that was explored in depth by Noether who formulated a ground-breaking theory that applies to all sizes of Matter. This theory applied to Biology can explain the origin of HGC as applied not only to animals developing along the A/P axis but also to animals with circular symmetry.

scholarly journals Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity

J ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 151-161
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Hox Genes ◽  
Fundamental Property ◽  
Gene Clusters ◽  
Strand Break ◽  
Early Embryo ◽  
Conserved Quantity ◽  
Biophysical Model ◽  
Self Similarity ◽  
Hox Gene ◽  
Hox Clusters

Hox Gene Collinearity (HGC) is a fundamental property that controls the development of many animal species, including vertebrates. In the Hox gene clusters, the genes are located in a sequential order Hox1, Hox2, Hox3, etc., along the 3’ to 5’ direction of the cluster in the chromosome. During Hox cluster activation, the Hox genes are expressed sequentially in the ontogenetic units D1, D2, D3, etc., along the anterior–posterior axis (A-P) of the early embryo. This collinearity, first observed by E.B. Lewis, is surprising because the spatial collinearity of these structures (Hox clusters and embryos) correlates entities that differ by about four orders of magnitude. Biomolecular mechanisms alone cannot explain such correlations. Long-range physical interactions, such as diffusion or electric attractions, should be involved. A biophysical model (BM) was formulated, which, in alignment with the biomolecular processes, successfully describes the existing vertebrate genetic engineering data. One hundred years ago, Emmy Noether made a fundamental discovery in mathematics and physics. She proved, rigorously, that a physical system obeying a symmetry law (e.g., rotations or self-similarity) is followed by a conserved physical quantity. It is argued here that HGC obeys a ‘primitive’ self-similarity symmetry. In this case, the associated primitive conserved quantity is the irreversibly increasing ‘ratchet’-like Hoxgene ordering where some genes may be missing. The genes of a vertebrate Hox clusterare located along a finite straight line. The same order follows the ontogenetic unitsof the vertebrate embryo. Therefore, HGC is a manifestation of a primitive Noether Theory (NT). NT may be applied to other than the vertebrate case, for instance, to animals with a circular topological symmetry. For example, the observed abnormal Hox gene ordering of the echinoderm Hox clusters may be reproduced by a double-strand break of the circular Hox gene ordering and its subsequent incorporation in the flanking chromosome.

scholarly journals Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

2021 ◽  
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Dna Sequence ◽  
Hox Genes ◽  
The Other ◽  
Biophysical Model ◽  
Hox Gene ◽  
Embryonic Tissues ◽  
Transcription Factory ◽  
Animal Phyla ◽  
Physical Forces ◽  
Hox Clusters

Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important during embryogenesis. It relates events occurring in Hox clusters inside the chromosome DNA and embryonic tissues. These two entities differ in size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order H1, H2, H3 … along the 3’ to 5’ direction of the DNA sequence. The corresponding embryonic tissues (E1, E2, E3, …) are activated along the Anterior – Posterior axis in the same order. Besides this collinearity a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is H1 expressed in E1, later is H2 in E2, followed by H3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) has been formulated and tested in the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. In the present work two equivalent realizations of BM are presented which explain the recent findings on TC as observed in the vertebrates.

scholarly journals Physical Laws shape up HOX Gene Collinearity

2021 ◽  
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Hox Genes ◽  
Biophysical Model ◽  
Hox Gene ◽  
Embryonic Tissues ◽  
Transcription Factory ◽  
Animal Phyla ◽  
Physical Forces ◽  
Physical Laws ◽  
Hox Clusters ◽  
Anterior Posterior

Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3’ to 5’ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior – Posterior axis of the embyo. Expression of Hox1 occurs in E1. Hox2 in E2, Hox3 in E3… Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is Hox1 expressed in E1, later is Hox2 expressed in E2, followed by Hox3 in E3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) was formulated and tested during the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. Symmetry is a physical-mathematical property of Matter that was explored in depth by Noether who formulated a ground-breaking theory that applies to all sizes of Matter. This theory applied to Biology can explain the origin of HGC as applied not only to animals developing along the A/P axis but also to animals with circular symmetry.

Analysis of Hox gene expression in the chick limb bud

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1449-1466 ◽  
Author(s):  
C.E. Nelson ◽  
B.A. Morgan ◽  
A.C. Burke ◽  
E. Laufer ◽  
E. DiMambro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Sonic Hedgehog ◽  
Hind Limb ◽  
Hox Genes ◽  
Expression Patterns ◽  
Limb Bud ◽  
Posterior Portion ◽  
Hox Gene ◽  
Hoxd Gene

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.

Gene loss and gain in the evolution of the vertebrates

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 155-161
Author(s):  
Frank H. Ruddle ◽  
Kevin L. Bentley ◽  
Michael T. Murtha ◽  
Neil Risch
Keyword(s):  
Hox Genes ◽  
Gene Loss ◽  
Biological Function ◽  
Hox Gene ◽  
Step Process ◽  
Gene Expansion ◽  
Multiple Clusters ◽  
Adaptive Role ◽  
Hox Clusters

Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.

scholarly journals Hox Gene Collinearity May Be Related to Noether’s Theory on Symmetry and Its Linked Conserved Quantities

2019 ◽  
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Hox Genes ◽  
Fundamental Property ◽  
Gene Clusters ◽  
Early Embryo ◽  
Biophysical Model ◽  
Self Similarity ◽  
Hox Gene ◽  
Hox Cluster ◽  
Straight Line ◽  
Physical Interactions

Hox Gene Collinearity (HGC) is a fundamental property that determines the development of many animal clades including Vertebrates. In the Hox gene clusters the genes are located in a sequence Hox1, Hox2, Hox3,… along the 3’ to 5’ direction of the cluster in the chromosome. During Hox cluster activation the Hox genes are expressed sequentially in the ontogenetic units D1, D2, D3,… along the anterior (A)- Posterior (P) axis of the early embryo. This collinearity, first observed by E.B. Lewis, is surprising because the spatial extent of these structures (Hox clusters and embryos) differ by about 4 orders of magnitude. Biomolecular mechanisms alone cannot explain this correlation. Long range physical interactions like diffusion or electric attractions should be involved. A biophysical model (BM) has been  formulated which cooperates with the biomolecular processes and describes the data successfully. Hundred years ago E. Noether made a fundamental discovery in Mathematics and Physics. She proved rigorously that a physical system obeying a symmetry law (e.g.rotations or self similarity) is linked to a conserved physical quantity. It is argued here that HGC obeys a ‘primitive’ self similarity symmetry of the genes of a Hox cluster along a finite straight line. In the case of Vertebrates, the associated partially conserved quantity is the ever increasing ‘ratchet’- like gene ordering where some Hox genes are missing. Another application of Noether’s Theory is performed to rotationally symmetric embryos like the sea urchin.

scholarly journals Physical Laws Shape Up HOX Gene Collinearity

2021 ◽  
Vol 9 (2) ◽  
pp. 17
Author(s):  
Spyros Papageorgiou
Keyword(s):  
Hox Genes ◽  
Biophysical Model ◽  
Scalar Property ◽  
Hox Gene ◽  
Embryonic Tissues ◽  
Transcription Factory ◽  
Animal Phyla ◽  
Physical Forces ◽  
Physical Laws ◽  
Anterior Posterior

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3′ to 5′ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior—Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical–mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry.

scholarly journals Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Daan Noordermeer ◽  
Marion Leleu ◽  
Patrick Schorderet ◽  
Elisabeth Joye ◽  
Fabienne Chabaud ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Hox Genes ◽  
Temporal Dynamics ◽  
Gene Products ◽  
Circular Chromosome ◽  
Chromosome Conformation ◽  
Hox Gene ◽  
Circular Chromosome Conformation Capture ◽  
Hox Clusters

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels.

Hox genes and growth: early and late roles in limb bud morphogenesis

Development ◽  
1994 ◽  
Vol 1994 (Supplement) ◽  
pp. 181-186
Author(s):  
Bruce A. Morgan ◽  
Cliff Tabin
Keyword(s):  
Limb Development ◽  
Hox Genes ◽  
Limb Bud ◽  
Limb Mesenchyme ◽  
Positional Identity ◽  
Limb Morphogenesis ◽  
Combined Action ◽  
Level Of Understanding ◽  
Hox Clusters ◽  
Hoxd Gene

In recent years, molecular analysis has led to the identification of some of the key genes that control the morphogenesis of the developing embryo. Detailed functional analysis of these genes is rapidly leading to a new level of understanding of how embryonic form is regulated. Understanding the roles that these genes play in development can additionally provide insights into the evolution of morphology. The 5′ genes of the vertebrate Hox clusters are expressed in complex patterns during limb morphogenesis. Various models suggest that the Hoxd genes specify positional identity along the anteroposterior (A-P) axis of the limb. Close examination of the pattern of Hoxd gene expression in the limb suggests that a distinct combination of Hoxd gene expressed in different digit primordia is unlikely to specify each digit independently. The effects of altering the pattern of expression of the Hoxd-11 gene at different times during limb development indicate that the Hoxd genes have separable early and late roles in limb morphogenesis. In their early role, the Hoxd genes are involved in regulating the growth of the undifferentiated limb mesenchyme. Restriction of the expression of successive 5′ Hoxd genes to progressively more posterior regions of the bud results in the asymmetric outgrowth of the limb mesenchyme. Later in limb development, Hoxd genes also regulate the maturation of the nascent skeletal elements. The degree of overlap in function between different Hoxd genes may be different in these early and late roles. The combined action of many Hox genes on distinct developmental processes contribute to pattern asymmetry along the A-P axis.

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