The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Robb Krumlauf - One of the best experts on this subject based on the ideXlab platform.
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conservation and elaboration of Hox Gene regulation during evolution of the vertebrate head
Nature, 2000Co-Authors: Miguel Manzanares, Paul A Trainor, Robb Krumlauf, Hiroshi Wada, Nobue Itasaki, Peter W H HollandAbstract:The comparison of Hox Genes between vertebrates and their closest invertebrate relatives (amphioxus and ascidia) highlights two derived features of Hox Genes in vertebrates: duplication of the Hox Gene cluster, and an elaboration of Hox expression patterns and roles compared with non-vertebrate chordates. We have investigated how new expression domains and their associated developmental functions evolved, by testing the cis-regulatory activity of genomic DNA fragments from the cephalochordate amphioxus Hox cluster in transgenic mouse and chick embryos. Here we present evidence for the conservation of cis-regulatory mechanisms controlling Gene expression in the neural tube for half a billion years of evolution, including a dependence on retinoic acid signalling. We also identify amphioxus Hox Gene regulatory elements that drive spatially localized expression in vertebrate neural crest cells, in derivatives of neurogenic placodes and in branchial arches, despite the fact that cephalochordates lack both neural crest and neurogenic placodes. This implies an elaboration of cis-regulatory elements in the Hox Gene cluster of vertebrate ancestors during the evolution of craniofacial patterning.
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patterning the cranial neural crest hinbrain segmentation and Hox Gene plasticity
Nature Reviews Neuroscience, 2000Co-Authors: Paul A Trainor, Robb KrumlaufAbstract:Understanding the patterning mechanisms that control head development — particularly the neural crest and its contribution to bones, nerves and connective tissue — is an important problem, as craniofacial anomalies account for one-third of all human congenital defects. Classical models for craniofacial patterning argue that the morphogenic program and Hox Gene identity of the neural crest is pre-patterned, carrying positional information acquired in the hindbrain to the peripheral nervous system and the branchial arches. Recently, however, plasticity of Hox Gene expression has been observed in the hindbrain and cranial neural crest of chick, mouse and zebrafish embryos. Hence, craniofacial development is not dependent on neural crest pre-patterning, but is regulated by a more complex integration of cell and tissue interactions.
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patterning the cranial neural crest hindbrain segmentation and Hox Gene plasticity
Nature Reviews Neuroscience, 2000Co-Authors: Paul A Trainor, Robb KrumlaufAbstract:Understanding the patterning mechanisms that control head development--particularly the neural crest and its contribution to bones, nerves and connective tissue--is an important problem, as craniofacial anomalies account for one-third of all human congenital defects. Classical models for craniofacial patterning argue that the morphogenic program and Hox Gene identity of the neural crest is pre-patterned, carrying positional information acquired in the hindbrain to the peripheral nervous system and the branchial arches. Recently, however, plasticity of Hox Gene expression has been observed in the hindbrain and cranial neural crest of chick, mouse and zebrafish embryos. Hence, craniofacial development is not dependent on neural crest prepatterning, but is regulated by a more complex integration of cell and tissue interactions.
David P Polly - One of the best experts on this subject based on the ideXlab platform.
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evolution of the snake body form reveals homoplasy in amniote Hox Gene function
Nature, 2015Co-Authors: Jason J. Head, David P PollyAbstract:Traditionally, the vertebral column of snakes was thought to have lost regionalization; Hox regionalization is now shown to be maintained in snakes, suggesting that gradational vertebral column regionalization is primitive to amniotes. It had been thought that the vertebral column of snakes has lost regionalization anterior to the cloaca, either because of homogenization of body-patterning Hox Gene codes or of their downstream effectors. Jason Head and David Polly turn received wisdom on its head, with a quantitative analysis of the vertebral column in snakes that shows not only is Hox regionalization maintained, but the morphology is too. This surprising finding suggests that regionalization is primitive to amniotes, even though that regionalization might be quite subtle. In which case, the more apparent regionalization in some archosaurs (crocodiles and birds) and in mammals could be a consequence of independent evolution in the Hox code, rather than representing the ancestral condition for clades with snake-like body forms. Hox Genes regulate regionalization of the axial skeleton in vertebrates1,2,3,4,5,6,7, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms8,9,10,11,12,13,14. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox Gene expression domains9, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions10,11,12,13. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phyloGenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped Gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox Gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior–posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number15, not by changes in the function of primaxial Hox Genes9,10.
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evolution of the snake body form reveals homoplasy in amniote Hox Gene function
Nature, 2015Co-Authors: Jason J. Head, David P PollyAbstract:Hox Genes regulate regionalization of the axial skeleton in vertebrates, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox Gene expression domains, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phyloGenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped Gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox Gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior-posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number, not by changes in the function of primaxial Hox Genes.
Jason J. Head - One of the best experts on this subject based on the ideXlab platform.
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evolution of the snake body form reveals homoplasy in amniote Hox Gene function
Nature, 2015Co-Authors: Jason J. Head, David P PollyAbstract:Traditionally, the vertebral column of snakes was thought to have lost regionalization; Hox regionalization is now shown to be maintained in snakes, suggesting that gradational vertebral column regionalization is primitive to amniotes. It had been thought that the vertebral column of snakes has lost regionalization anterior to the cloaca, either because of homogenization of body-patterning Hox Gene codes or of their downstream effectors. Jason Head and David Polly turn received wisdom on its head, with a quantitative analysis of the vertebral column in snakes that shows not only is Hox regionalization maintained, but the morphology is too. This surprising finding suggests that regionalization is primitive to amniotes, even though that regionalization might be quite subtle. In which case, the more apparent regionalization in some archosaurs (crocodiles and birds) and in mammals could be a consequence of independent evolution in the Hox code, rather than representing the ancestral condition for clades with snake-like body forms. Hox Genes regulate regionalization of the axial skeleton in vertebrates1,2,3,4,5,6,7, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms8,9,10,11,12,13,14. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox Gene expression domains9, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions10,11,12,13. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phyloGenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped Gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox Gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior–posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number15, not by changes in the function of primaxial Hox Genes9,10.
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evolution of the snake body form reveals homoplasy in amniote Hox Gene function
Nature, 2015Co-Authors: Jason J. Head, David P PollyAbstract:Hox Genes regulate regionalization of the axial skeleton in vertebrates, and changes in their expression have been proposed to be a fundamental mechanism driving the evolution of new body forms. The origin of the snake-like body form, with its deregionalized pre-cloacal axial skeleton, has been explained as either homogenization of Hox Gene expression domains, or retention of standard vertebrate Hox domains with alteration of downstream expression that suppresses development of distinct regions. Both models assume a highly regionalized ancestor, but the extent of deregionalization of the primaxial domain (vertebrae, dorsal ribs) of the skeleton in snake-like body forms has never been analysed. Here we combine geometric morphometrics and maximum-likelihood analysis to show that the pre-cloacal primaxial domain of elongate, limb-reduced lizards and snakes is not deregionalized compared with limbed taxa, and that the phyloGenetic structure of primaxial morphology in reptiles does not support a loss of regionalization in the evolution of snakes. We demonstrate that morphometric regional boundaries correspond to mapped Gene expression domains in snakes, suggesting that their primaxial domain is patterned by a normally functional Hox code. Comparison of primaxial osteology in fossil and modern amniotes with Hox Gene distributions within Amniota indicates that a functional, sequentially expressed Hox code patterned a subtle morphological gradient along the anterior-posterior axis in stem members of amniote clades and extant lizards, including snakes. The highly regionalized skeletons of extant archosaurs and mammals result from independent evolution in the Hox code and do not represent ancestral conditions for clades with snake-like body forms. The developmental origin of snakes is best explained by decoupling of the primaxial and abaxial domains and by increases in somite number, not by changes in the function of primaxial Hox Genes.
Clifford J. Tabin - One of the best experts on this subject based on the ideXlab platform.
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In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox Gene regulation
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Edwina Mcglinn, Soraya Yekta, Jennifer H. Mansfield, Jürgen Soutschek, David P. Bartel, Clifford J. TabinAbstract:Patterning of the vertebrate axial skeleton requires precise spatial and temporal control of Hox Gene expression during embryonic development. MicroRNAs (miRNAs) are recently described modulators of Gene activity, and members of the miR-196 and miR-10 families have been shown to target several Hox Genes in vivo. Testing miRNA function in mice is complicated by potential redundancy between family members. To circumvent this, we have developed protocols for introducing modified antisense oligonucleotides (antagomiRs) in ovo during chick development. Using this approach, we identify a layer of regulatory control provided by the miR-196 family in defining the boundary of Hox Gene expression along the anterior-posterior (A-P) embryonic axis. Following knockdown of miR-196, we observe a homeotic transformation of the last cervical vertebrae toward a thoracic identity. This phenotypic alteration is, in part, due to an anterior expansion of Hoxb8 Gene expression and consolidates the in vivo relevance of post-transcriptional Hox Gene regulation provided by miRNAs in the complex hierarchies governing axial pattering.
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goosecoid misexpression alters the morphology and Hox Gene expression of the developing chick limb bud
Mechanisms of Development, 1997Co-Authors: Tiffany A Heanue, Randy L Johnson, Juan Carlos Izpisuabelmonte, Claudio D Stern, Edward M De Robertis, Clifford J. TabinAbstract:The homeobox-containing Gene goosecoid (gsc) has been implicated in a variety of embryonic processes from gastrulation to rib patterning. We have analyzed the role it plays during chick limb development. Expression is initially observed at stage 20 in a proximal-anterior-ventral domain of the early limb bud which expands during subsequent stages. Later in limb development a second domain of expression appears distally which resolves to regions which surround the condensing cartilage. In order to understand the function of gsc in limb development, we have examined the effect of misexpressing gsc throughout the limb. Two striking phenotypes are observed. The first, evident at stage 24, is an alteration in the angle of femur outgrowth from the main body axis. The second, which can be detected at day 10 of development, is an overall decrease in the size of the limb with bones that are small, misshapen and bent. These phenotypes correlate with a decrease in levels of Hox Gene expression in gsc-infected limb buds. From these results we suggest that gsc may normally function to regulate growth and patterning of the limb, perhaps through regulation of Hox Gene expression.
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analysis of Hox Gene expression in the chick limb bud
Development, 1996Co-Authors: Craig E Nelson, Bruce A Morgan, Ann C Burke, Ed Laufer, E Dimambro, Lewis C Murtaugh, E Gonzales, Lino Tessarollo, Luis F Parada, Clifford J. TabinAbstract: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.
Denis Duboule - One of the best experts on this subject based on the ideXlab platform.
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temporal dynamics and developmental memory of 3d chromatin architecture at Hox Gene loci
eLife, 2014Co-Authors: Daan Noordermeer, Denis Duboule, Marion Leleu, Patrick Schorderet, Elisabeth Joye, Fabienne ChabaudAbstract:Most animals are symmetrical about an imaginary line that runs from the head to the tail. A family of Genes called the Hox family ensures that the cells in an animal embryo develop into the correct body parts along this head-to-tail axis. Hox Genes—which are found in animals as diverse as flies and humans—are often clustered on the chromosomes, and their order within a cluster affects when and where each Hox Gene is ‘switched on’. In mammals, Hox Genes at one end of a cluster are switched on first and along almost the entire length of the embryo. Hox Genes near the other end of the cluster are expressed later and only towards the hind end of the animal. And Hox Genes at the furthest end of the cluster are expressed last and in the very tip of the developing tail. The time when a Hox Gene is expressed depends largely on its relative position within the Gene cluster. However, it is not clear how the ordering of the Genes within a cluster is translated into a schedule whereby the Genes are sequentially switched on during development. Much of the DNA in a chromosome is wrapped around proteins to form a structure called chromatin; chromatin is normally tightly packed, but ‘unpacking’ it allows the Genes to be accessed and switched on. Now, Noordermeer et al. have used a technique called ‘circular chromosome conformation capture’ to follow how the packing of the chromosomes that carry the Hox Gene clusters changes during embryonic development. Harvesting cells from mouse embryos of different ages, and cross-linking the DNA to the proteins, allowed those Genes that are packed in the chromatin to be distinguished from those that have been unpacked and activated. When the embryo is still just a ball of almost identical cells, all the Hox Genes are switched off and packed into inactive chromatin. However, Noordermeer et al. found that, as the embryo develops and when each Hox Gene is switched on in turn, the relevant region of DNA is also unpacked and moved into more active chromatin. This mechanism likely prevents Hox Genes that direct the development of the hind end of the mouse from being switched on too early, and hence it avoids body parts being misidentified and developing incorrectly. Further, the patterns of active chromatin vs inactive chromatin can be fixed at each section along head-to-tail axis, such that it will be memorized in all daughter cells produced subsequently from each particular body section. Future challenges will be to uncover the trigger behind the step-wise transition of every Hox Gene from inactive chromatin to active chromatin, and to crack the underlying ‘clock’ that controls the timing of this process.
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The dynamic architecture of Hox Gene clusters
Science, 2011Co-Authors: Daan Noordermeer, Erik Splinter, Jacques Rougemont, Marion Leleu, Wouter De Laat, Denis DubouleAbstract:The spatial and temporal control of Hox Gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox Genes are active. When the cluster is transcriptionally inactive, Hox Genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated Genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the Gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the colinear activation of these compact Gene clusters.
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the rise and fall of Hox Gene clusters
Development, 2007Co-Authors: Denis DubouleAbstract: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.
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Hox Gene expression in teleost fins and the origin of vertebrate digits
Nature, 1995Co-Authors: Paolo Sordino, F Van Der Hoeven, Denis DubouleAbstract:Hox Genes are essential for growth and patterning of the tetrapod limb skeleton. Mice mutant for the Hoxd-13 Gene have an important delay in morphoGenesis owing to reduced proliferation. Based on the appearance of atavisms in such mice, we suggested that modifications of Hox Gene regulation may have been a source of morphological variation during the evolution of tetrapod limbs. Pectoral and pelvic fins are homologous to fore- and hindlimbs, respectively. To compare the relative importance of Hox Genes during fin versus limb morphoGenesis, we cloned zebrafish (Danio rerio) HoxD and HoxA complex Genes and analysed their expression during fin development. The results suggest a scheme for the fin-limb transition in which the distal autopods (digits) are neomorphic structures produced by unequal proliferation of the posterior part of an ancestral appendix.