The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
A. J. Durston - One of the best experts on this subject based on the ideXlab platform.
-
some questions and answers about the role of hox temporal collinearity in vertebrate Axial Patterning
Frontiers in Cell and Developmental Biology, 2019Co-Authors: A. J. DurstonAbstract:The vertebrate anterior-posterior (A-P = craniocaudal) axis is evidently made by a timing mechanism. Evidence has accumulated that tentatively identifies the A-P timer as being or involving Hox temporal collinearity (TC). Here, I focus on the two current competing models based on this premise. Common features and points of dissent are examined and a common model is distilled from what remains. This is an attempt to make sense of the literature.
-
two tier hox collinearity mediates vertebrate Axial Patterning
Frontiers in Cell and Developmental Biology, 2018Co-Authors: A. J. DurstonAbstract:A two tier mechanism mediates Hox collinearity. Besides the familiar collinear chromatin modification within each Hox cluster (nanocollinearity), there is also a macrocollinearity tier. Individual Hox clusters and individual cells are coordinated and synchronized to generate multiscale (macro and nano) collinearity in the early vertebrate embryo. Macro-collinearity is mediated by three non-cell autonomous Hox-Hox interactions. These mediate temporal collinearity in early NOM (non-organizer mesoderm), time space translation where temporal collinearity is translated to spatial collinearity along the early embryo's main body axis and neural transformation, where Hox expression is copied monospecifically from NOM mesoderm to overlying neurectoderm in the late gastrula. Unlike nanocollinearity, which is Hox cluster restricted, Axial macrocollinearity extends into the head and EAD domains, thus covering the whole embryonic anterior-posterior (A-P) axis. EAD: extreme anterior domain, the only A-P Axial domain anterior to the head. The whole time space translation mechanism interacts with A-P signaling pathways via "decision points," separating different domains on the axis.
-
a time space translation hypothesis for vertebrate Axial Patterning
Seminars in Cell & Developmental Biology, 2015Co-Authors: A. J. Durston, K ZhuAbstract:How vertebrates generate their anterior-posterior axis is a >90-year-old unsolved probem. This mechanism clearly works very differently in vertebrates than in Drosophila. Here, we present evidence from the Amphibian Xenopus that a time space translation mechanism underlies initial Axial Patterning in the trunk part of the axis. We show that a timer in the gastrula's non organiser mesoderm (NOM) undergoes sequential timed interactions with the Spemann organiser (SO) during gastrulation to generate the spatial Axial pattern. Evidence is also presented that this mechanism works via Hox collinearity and that it requires Hox functionality. The NOM timer is putatively Hox temporal collinearity. This generates a spatially collinear Axial Hox pattern in the emerging dorsal central nervous system and dorsal parAxial mesoderm. The interactions with the organiser are mediated by a BMP-anti BMP dependent mechanism. Hox functionality is implicated because knocking out the Hox1 paralogue group not only disrupts expression of Hox1 genes but also of the whole spatially collinear Axial Hox sequence in the early embryo's A-P axis. This mechanism and its nature are discussed. The evidence supporting this hypothesis is presented and critically assessed. Strengths and weaknesses, questions, uncertainties and holes in the evidence are identified. Future directions are indicated.
-
review time space translation regulates trunk Axial Patterning in the early vertebrate embryo
Genomics, 2010Co-Authors: A. J. Durston, Hans J Jansen, Stephan A WackerAbstract:Abstract Here, 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 non-organiser mesoderm and the Spemann organiser. The timer is characterised by temporally colinear activation of a series of Hox genes in the early ventral and lateral mesoderm (i.e., the non-organiser mesoderm) of the Xenopus gastrula. This early Hox gene expression is transient, unless it is stabilised by signals from the Spemann organiser. The non-organiser mesoderm (NOM) and the Spemann organiser undergo timed interactions during gastrulation which lead to the formation of an anterior–posterior axis and stable Hox gene expression. When separated from each other, neither non-organiser mesoderm nor the Spemann organiser is able to induce anterior–posterior pattern formation of the trunk. We present a model describing that NOM acquires transiently stable hox codes and spatial colinearity after involution into the gastrula and that convergence and extension then continually bring new cells from the NOM within the range of organiser 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 non-organiser mesoderm, but not the age of the organiser, defines positional values along the anterior–posterior axis. We postulate that the temporal information from the non-organiser mesoderm is linked to mesodermal Hox expression. The role of the organiser was investigated further and this turns out to be only the induction of neural tissue. Apparently, development of a stable Axial hox pattern requires neural hox Patterning.
-
Axial Patterning in snakes and caecilians evidence for an alternative interpretation of the hox code
Developmental Biology, 2009Co-Authors: Joost M Woltering, Freek J Vonk, Hendrik Muller, Nabila Bardine, Ioana Laura Tuduce, Merijn A G De Bakker, Walter Knochel, Ovidiu I Sirbu, A. J. DurstonAbstract:It is generally assumed that the characteristic deregionalized body plan of species with a snake-like morphology evolved through a corresponding homogenization of Hox gene expression domains along the primary axis. Here, we examine the expression of Hox genes in snake embryos and show that a collinear pattern of Hox expression is retained within the parAxial mesoderm of the trunk. Genes expressed at the anterior and most posterior, regionalized, parts of the skeleton correspond to the expected anatomical boundaries. Unexpectedly however, also the dorsal (thoracic), homogenous rib-bearing region of trunk, is regionalized by unconventional gradual anterior limits of Hox expression that are not obviously reflected in the skeletal anatomy. In the lateral plate mesoderm we also detect regionalized Hox expression yet the forelimb marker Tbx5 is not restricted to a rudimentary forelimb domain but is expressed throughout the entire flank region. Analysis of several Hox genes in a caecilian amphibian, which convergently evolved a deregionalized body plan, reveals a similar global collinear pattern of Hox expression. The differential expression of posterior, vertebra-modifying or even rib-suppressing Hox genes within the dorsal region is inconsistent with the homogeneity in vertebral identity. Our results suggest that the evolution of a deregionalized, snake-like body involved not only alterations in Hox gene cis-regulation but also a different downstream interpretation of the Hox code.
Mary C Mullins - One of the best experts on this subject based on the ideXlab platform.
-
the bmp signaling gradient is interpreted through concentration thresholds in dorsal ventral Axial Patterning
PLOS Biology, 2021Co-Authors: Hannah Greenfeld, Jerome Lin, Mary C MullinsAbstract:Bone Morphogenetic Protein (BMP) patterns the dorsal-ventral (DV) embryonic axis in all vertebrates, but it is unknown how cells along the DV axis interpret and translate the gradient of BMP signaling into differential gene activation that will give rise to distinct cell fates. To determine the mechanism of BMP morphogen interpretation in the zebrafish gastrula, we identified 57 genes that are directly activated by BMP signaling. By using Seurat analysis of single-cell RNA sequencing (scRNA-seq) data, we found that these genes are expressed in at least 3 distinct DV domains of the embryo. We distinguished between 3 models of BMP signal interpretation in which cells activate distinct gene expression through interpretation of thresholds of (1) the BMP signaling gradient slope; (2) the BMP signal duration; or (3) the level of BMP signal activation. We tested these 3 models using quantitative measurements of phosphorylated Smad5 (pSmad5) and by examining the spatial relationship between BMP signaling and activation of different target genes at single-cell resolution across the embryo. We found that BMP signaling gradient slope or BMP exposure duration did not account for the differential target gene expression domains. Instead, we show that cells respond to 3 distinct levels of BMP signaling activity to activate and position target gene expression. Together, we demonstrate that distinct pSmad5 threshold levels activate spatially distinct target genes to pattern the DV axis.
-
Maternal and Zygotic Control of Zebrafish Dorsoventral Axial Patterning
Annual Review of Genetics, 2011Co-Authors: Yvette G. Langdon, Mary C MullinsAbstract:Vertebrate development begins with precise molecular, cellular, and morphogenetic controls to establish the basic body plan of the embryo. In zebrafish, these tightly regulated processes begin during oogenesis and proceed through gastrulation to establish and pattern the axes of the embryo. During oogenesis a maternal factor is localized to the vegetal pole of the oocyte that is a determinant of dorsal tissues. Following fertilization this vegetally localized dorsal determinant is asymmetrically translocated in the egg and initiates formation of the dorsoventral axis. Dorsoventral axis formation and Patterning is then mediated by maternal and zygotic factors acting through Wnt, BMP (bone morphogenetic protein), Nodal, and FGF (fibroblast growth factor) signaling pathways, each of which is required to establish and/or pattern the dorsoventral axis. This review addresses recent advances in our understanding of the molecular factors and mechanisms that establish and pattern the dorsoventral axis of the zebrafish embryo, including establishment of the animal-vegetal axis as it relates to formation of the dorsoventral axis.
-
twisted gastrulation promotes bmp signaling in zebrafish dorsal ventral Axial Patterning
Development, 2004Co-Authors: Shawn C Little, Mary C MullinsAbstract:In vertebrates and invertebrates, the bone morphogenetic protein (BMP) signaling pathway patterns cell fates along the dorsoventral (DV) axis. In vertebrates, BMP signaling specifies ventral cell fates, whereas restriction of BMP signaling by extracellular antagonists allows specification of dorsal fates. In misexpression assays, the conserved extracellular factor Twisted gastrulation (Tsg) is reported to both promote and antagonize BMP signaling in DV Patterning. To investigate the role of endogenous Tsg in early DV Patterning, we performed morpholino (MO)-based knockdown studies of Tsg1 in zebrafish. We found that loss of tsg1 results in a moderately strong dorsalization of the embryonic axis, suggesting that Tsg1 promotes ventral fates. Knockdown of tsg1 combined with loss of function of the BMP agonist tolloid ( mini fin ) or heterozygosity for the ligand bmp2b ( swirl ) enhanced dorsalization, supporting a role for Tsg1 in specifying ventral cell fates as a BMP signaling agonist. Moreover, loss of tsg1 partially suppressed the ventralized phenotypes of mutants of the BMP antagonists Chordin or Sizzled (Ogon). Our results support a model in which zebrafish Tsg1 promotes BMP signaling, and thus ventral cell fates, during DV Axial Patterning.
Nadeem Moghal - One of the best experts on this subject based on the ideXlab platform.
-
neurons refine the caenorhabditis elegans body plan by directing Axial Patterning by wnts
PLOS Biology, 2013Co-Authors: Katarzyna Modzelewska, Amara Lauritzen, Stefan Hasenoeder, Louise Brown, John Georgiou, Nadeem MoghalAbstract:Metazoans display remarkable conservation of gene families, including growth factors, yet somehow these genes are used in different ways to generate tremendous morphological diversity. While variations in the magnitude and spatio-temporal aspects of signaling by a growth factor can generate different body patterns, how these signaling variations are organized and coordinated during development is unclear. Basic body plans are organized by the end of gastrulation and are refined as limbs, organs, and nervous systems co-develop. Despite their proximity to developing tissues, neurons are primarily thought to act after development, on behavior. Here, we show that in Caenorhabditis elegans, the axonal projections of neurons regulate tissue progenitor responses to Wnts so that certain organs develop with the correct morphology at the right Axial positions. We find that foreshortening of the posteriorly directed axons of the two canal-associated neurons (CANs) disrupts mid-body vulval morphology, and produces ectopic vulval tissue in the posterior epidermis, in a Wnt-dependent manner. We also provide evidence that suggests that the posterior CAN axons modulate the location and strength of Wnt signaling along the anterior–posterior axis by employing a Ror family Wnt receptor to bind posteriorly derived Wnts, and hence, refine their distributions. Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in Patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1. Thus, unmyelinated axon tracts are critical for Patterning the C. elegans body. Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.
Hans R Bode - One of the best experts on this subject based on the ideXlab platform.
-
Axial Patterning in hydra
Cold Spring Harbor Perspectives in Biology, 2009Co-Authors: Hans R BodeAbstract:Morphogen gradients play an important role in pattern formation during early stages of embryonic development in many bilaterians. In an adult hydra, Axial Patterning processes are constantly active because of the tissue dynamics in the adult. These processes include an organizer region in the head, which continuously produces and transmits two signals that are distributed in gradients down the body column. One signal sets up and maintains the head activation gradient, which is a morphogenetic gradient. This gradient confers the capacity of head formation on tissue of the body column, which takes place during bud formation, hydra's mode of asexual reproduction, as well as during head regeneration following bisection of the animal anywhere along the body column. The other signal sets up the head inhibition gradient, which prevents head formation, thereby restricting bud formation to the lower part of the body column in an adult hydra. Little is known about the molecular basis of the two gradients. In contrast, the canonical Wnt pathway plays a central role in setting up and maintaining the head organizer.
-
formation of the head organizer in hydra involves the canonical wnt pathway
Development, 2005Co-Authors: Mariya Broun, Beate Reinhardt, Lydia Gee, Hans R BodeAbstract:Stabilization of β-catenin by inhibiting the activity of glycogen synthase kinase-3β has been shown to initiate axis formation or Axial Patterning processes in many bilaterians. In hydra, the head organizer is located in the hypostome, the apical portion of the head. Treatment of hydra with alsterpaullone, a specific inhibitor of glycogen synthase kinase-3β, results in the body column acquiring characteristics of the head organizer, as measured by transplantation experiments, and by the expression of genes associated with the head organizer. Hence, the role of the canonical Wnt pathway for the initiation of axis formation was established early in metazoan evolution.
-
hybmp5 8b a bmp5 8 orthologue acts during Axial Patterning and tentacle formation in hydra
Developmental Biology, 2004Co-Authors: Beate Reinhardt, Mariya Broun, Ira L Blitz, Hans R BodeAbstract:Developmental gradients play a central role in Axial Patterning in hydra. As part of the effort towards elucidating the molecular basis of these gradients as well as investigating the evolution of the mechanisms underlying Axial Patterning, genes encoding signaling molecules are under investigation. We report the isolation and characterization of HyBMP5-8b, a BMP5-8 orthologue, from hydra. Processes governing Axial Patterning are continuously active in adult hydra. Expression patterns of HyBMP5-8b in normal animals and during bud formation, hydra's asexual form of reproduction, were examined. These patterns, coupled with changes in patterns of expression in manipulated tissues during head regeneration, foot regeneration as well as under conditions that alter the positional value gradient indicate that the gene is active in two different processes. The gene plays a role in tentacle formation and in Patterning the lower end of the body axis.
-
The Role of Hox Genes in Axial Patterning in Hydra1
American Zoologist, 2001Co-Authors: Hans R BodeAbstract:Abstract Hox genes in bilaterians specify distinct regions along the anterior-posterior axis. A question of interest is when in metazoan evolution did this class of genes take on this function. Hox genes have been isolated from a number of cnidarian species including hydra. The expression patterns of two of them, Cnox-3 and Cnox-2 have been examined in adult hydra. Cnox-3, a labial homologue, plays a role in oral/anterior Patterning, while Cnox-2, a Deformed homologue or a Gsx homologue of the ParaHox cluster appears to repress anterior Patterning in the body column. The two genes play a role in Axial Patterning that is consistent with the tissue dynamics of an adult hydra.
-
hyalx an aristaless related gene is involved in tentacle formation in hydra
Development, 2000Co-Authors: Kerry M Smith, Lydia Gee, Hans R BodeAbstract:Developmental gradients are known to play important roles in Axial Patterning in hydra. Current efforts are directed toward elucidating the molecular basis of these gradients. We report the isolation and characterization of HyAlx, an aristaless-related gene in hydra. The expression patterns of the gene in adult hydra, as well as during bud formation, head regeneration and the formation of ectopic head structures along the body column, indicate the gene plays a role in the specification of tissue for tentacle formation. The use of RNAi provides more direct evidence for this conclusion. The different patterns of HyAlx expression during head regeneration and bud formation also provide support for a recent version of a reaction-diffusion model for Axial Patterning in hydra.
Takayuki Onai - One of the best experts on this subject based on the ideXlab platform.
-
canonical wnt β catenin and notch signaling regulate animal vegetal Axial Patterning in the cephalochordate amphioxus
Evolution & Development, 2019Co-Authors: Takayuki OnaiAbstract:: In bilaterians, animal/vegetal Axial (A/V) Patterning is a fundamental early developmental event for establishment of animal/vegetal polarity and following specification of the germ layers (ectoderm, mesoderm, endoderm), of which the evolutionary origin is enigmatic. Understanding A/V Axial Patterning in a basal animal from each phylum would help to reconstruct the ancestral state of germ layer specification in bilaterians and thus, the evolution of mesoderm, the third intermediate cell layer. Herein, data show that the canonical Wnt/β-catenin (cWnt) and Notch signaling pathways control mesoderm specification from the early endomesoderm in the basal chordate amphioxus. Amphioxus belongs to the deuterostome, one of the main superphyla in Bilateria. In the present study, genes (tcf, dsh, axin, gsk3β) encoding cWnt components were expressed in the endomesoderm during the gastrula stages. Excess cWnt signaling by BIO, a GSK3 inhibitor, expanded the expression domains of outer endomesodermal genes that include future mesodermal ones and suppressed inner endomesodermal and ectodermal genes. Interfering Notch signaling by DAPT, a γ-secretase inhibitor, resulted in decreased expression of ectodermal and endomesodermal markers. These results suggest that cWnt and Notch have important roles in mesoderm specification in amphioxus embryos. The evolution of the mesoderm is also discussed.
-
opposing nodal vg1 and bmp signals mediate Axial Patterning in embryos of the basal chordate amphioxus
Developmental Biology, 2010Co-Authors: Takayuki Onai, Ira L Blitz, Ken W Y Cho, Linda Z. HollandAbstract:The basal chordate amphioxus resembles vertebrates in having a dorsal, hollow nerve cord, a notochord and somites. However, it lacks extensive gene duplications, and its embryos are small and gastrulate by simple invagination. Here we demonstrate that Nodal/Vg1 signaling acts from early cleavage through the gastrula stage to specify and maintain dorsal/anterior development while, starting at the early gastrula stage, BMP signaling promotes ventral/posterior identity. Knockdown and gain-of-function experiments show that these pathways act in opposition to one another. Signaling by these pathways is modulated by dorsally and/or anteriorly expressed genes including Chordin, Cerberus, and Blimp1. Overexpression and/or reporter assays in Xenopus demonstrate that the functions of these proteins are conserved between amphioxus and vertebrates. Thus, a fundamental genetic mechanism for Axial Patterning involving opposing Nodal and BMP signaling is present in amphioxus and probably also in the common ancestor of amphioxus and vertebrates or even earlier in deuterostome evolution.
