scholarly journals Cdx1andCdx2have overlapping functions in anteroposterior patterning and posterior axis elongation

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2181-2193 ◽  
Author(s):  
Eric van den Akker ◽  
Sylvie Forlani ◽  
Kallayanee Chawengsaksophak ◽  
Wim de Graaff ◽  
Felix Beck ◽  
...  
Keyword(s):  
Vertebral Column ◽  
Hox Genes ◽  
Early Embryo ◽  
Paraxial Mesoderm ◽  
Thoracic Vertebrae ◽  
Tail Bud ◽  
Anteroposterior Patterning ◽  
C Elegans ◽  
Axis Elongation ◽  
Posterior Shift

Mouse Cdx and Hox genes presumably evolved from genes on a common ancestor cluster involved in anteroposterior patterning. Drosophila caudal (cad) is involved in specifying the posterior end of the early embryo, and is essential for patterning tissues derived from the most caudal segment, the analia. Two of the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like manner in the three germ layers. In the nascent paraxial mesoderm, both genes are expressed in cells contributing first to the most rostral, and then to progressively more caudal parts of the vertebral column. Later, expression regresses from the anterior sclerotomes, and is only maintained for Cdx1 in the dorsal part of the somites, and for both genes in the tail bud. Cdx1 null mutants show anterior homeosis of upper cervical and thoracic vertebrae. Cdx2-null embryos die before gastrulation, and Cdx2 heterozygotes display anterior transformations of lower cervical and thoracic vertebrae. We have analysed the genetic interactions between Cdx1 and Cdx2 in compound mutants. Combining mutant alleles for both genes gives rise to anterior homeotic transformations along a more extensive length of the vertebral column than do single mutations. The most severely affected Cdx1 null/Cdx2 heterozygous mice display a posterior shift of their cranio-cervical, cervico-thoracic, thoraco-lumbar, lumbo-sacral and sacro-caudal transitions. The effects of the mutations in Cdx1 and Cdx2 were co-operative in severity, and a more extensive posterior shift of the expression of three Hox genes was observed in double mutants. The alteration in Hox expression boundaries occurred early. We conclude that both Cdx genes cooperate at early stages in instructing the vertebral progenitors all along the axis, at least in part by setting the rostral expression boundaries of Hox genes. In addition, Cdx mutants transiently exhibit alterations in the extent of Hox expression domains in the spinal cord, reminding of the strong effects of overexpressing Cdx genes on Hox gene expression in the neurectoderm. Phenotypical alterations in the peripheral nervous system were observed at mid-gestation stages. Strikingly, the altered phenotype at caudal levels included a posterior truncation of the tail, mildly affecting Cdx2 heterozygotes, but more severely affecting Cdx1/Cdx2 double heterozygotes and Cdx1 null/Cdx2 heterozygotes. Mutations in Cdx1 and Cdx2 therefore also interfere with axis elongation in a cooperative way. The function of Cdx genes in morphogenetic processes during gastrulation and tail bud extension, and their relationship with the Hox genes are discussed in the light of available data in Amphioxus, C. elegans, Drosophila and mice.

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.

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3201-3211 ◽  
Author(s):  
C. Miller ◽  
D.A. Sassoon
Keyword(s):  
Reproductive Tract ◽  
Hox Genes ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Molecular Characteristics ◽  
Anteroposterior Patterning ◽  
Stratified Epithelium ◽  
Distinct Cell ◽  
Hoxa Gene Expression ◽  
Posterior Shift

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350–353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

scholarly journals Lineage tracing axial progenitors using Nkx1.2CreERT2 mice defines their trunk and tail contributions

2018 ◽  
Author(s):  
Aida Rodrigo Albors ◽  
Pamela A. Halley ◽  
Kate G. Storey
Keyword(s):  
Spinal Cord ◽  
Lineage Tracing ◽  
Paraxial Mesoderm ◽  
Mouse Line ◽  
Tail Bud ◽  
Dynamic Nature ◽  
Transgenic Mouse Line ◽  
Continuous Generation ◽  
Axis Elongation

AbstractThe vertebrate body forms by continuous generation of new tissue from progenitors at the posterior end of the embryo. In mice, these axial progenitors initially reside in the epiblast, from where they form the trunk; and later relocate to the chordo-neural hinge of the tail bud to form the tail. Among them, a small group of bipotent neuromesodermal progenitors (NMPs) are thought to generate the spinal cord and paraxial mesoderm to the end of axis elongation. The study of these progenitors, however, has proven challenging in vivo due to their small numbers and dynamic nature, and the lack of a unique molecular marker to identify them. Here, we report the generation of the Nkx1.2CreERT2 transgenic mouse line in which the endogenous Nkx1.2 promoter drives tamoxifen-inducible CreERT2 recombinase. We show that Nkx1.2CreERT2 targets axial progenitors, including NMPs and early neural and mesodermal progenitors. Using a YFP reporter, we demonstrate that Nkx1.2-expressing epiblast cells contribute to all three germ layers, mostly neuroectoderm and mesoderm excluding notochord; and continue contributing neural and paraxial mesoderm tissues from the tail bud. This study identifies the Nkx1.2-expressing cell population as the source of most trunk and tail tissues in the mouse; and provides a key tool to genetically label and manipulate this progenitor population in vivo.

scholarly journals Hox genes control vertebrate body elongation by collinear Wnt repression

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Nicolas Denans ◽  
Tadahiro Iimura ◽  
Olivier Pourquié
Keyword(s):  
Transcription Factor ◽  
Retinoic Acid ◽  
Hox Genes ◽  
Tail Bud ◽  
Progressive Reduction ◽  
Body Formation ◽  
Slowing Down ◽  
Somite Formation ◽  
Axis Elongation ◽  
Elongation Process

In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9–13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.

scholarly journals Natural Orifice Translumenal Endoscopic Surgery for Anterior Spinal Procedures

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Priscilla Magno ◽  
Mouen A. Khashab ◽  
Manuel Mas ◽  
Samuel A. Giday ◽  
Jonathan M. Buscaglia ◽  
...  
Keyword(s):  
Thoracic Spine ◽  
Endoscopic Surgery ◽  
Vertebral Column ◽  
Bone Biopsy ◽  
Posterior Mediastinum ◽  
Direct Access ◽  
Thoracic Vertebrae ◽  
Natural Orifice ◽  
Vertebral Bone ◽  
Vertebral Bodies

Background. NOTES techniques allow transesophageal access to the mediastinum. The aim of this study was to assess the feasibility of transesophageal biopsy of thoracic vertebrae.Methods. Nonsurvival experiments on four 50-kg porcine animals were performed. Transesophageal access to the mediastinum was attained using submucosal tunneling technique.Results. The posterior mediastinum was successfully accessed and navigated in all animals. Vertebral bodies and intervertebral spaces were easily approached while avoiding damage to adjacent vessels. Bone biopsy was successfully performed without complications, but the hardness of bone tissue resulted in small and fragmented samples.Conclusions. Peroral transesophageal access into the posterior mediastinum and thoracic vertebral bone biopsy was feasible and safe. The proximity of the esophagus to the vertebral column provides close and direct access to the thoracic spine and opens up new ground for the performance of multilevel anterior spine procedures using NOTES techniques.

scholarly journals The descending thoracic aorta morphological characteristics

2016 ◽  
Vol 22 (3) ◽  
pp. 186-191
Author(s):  
S. Malik ◽  
P. Bordei ◽  
A. Rusali ◽  
D. M. Iliescu
Keyword(s):  
Thoracic Aorta ◽  
Vertebral Body ◽  
Vertebral Column ◽  
Morphological Characteristics ◽  
Male Gender ◽  
Thoracic Vertebra ◽  
Thoracic Vertebrae ◽  
Lower Edge ◽  
Descending Thoracic Aorta ◽  
Left Flank

Abstract Our study was conducted by consulting angioCT sites made on a CT GE LightSpeed VCT64 Slice CT and a CT GE LightSpeed 16 Slice CT, following the path and relationships of the descending thoracic aorta against the vertebral column, outside diameters thereof at the thoracic vertebrae T4, T7, T12 and posterior intercostal arteries characteristics. The origin of of the descending thoracic aorta we found most commonly on the left flank of the lower edge of the vertebral body T4, but I have encountered cases where it had come above the lower edge of T4 on level of intervertebral disc T4-T5 or even at the upper edge of T5 vertebral body. At thoracic vertebra T4, on a total of 30 cases, the descending thoracic aorta present a diameter of 20.0 to 32.6 mm, values that correspond to male gender and to females diameter ranging from 25.5 to 27, 4 mm. At level of T7 thoracic vertebra, thoracic aorta present a diameter of 19.6 to 29.5 mm, values found in men, in women the diameter being from 21.9 to 25.2 mm. At thoracic vertebra T12, on a total of 27 cases, the descending thoracic aorta present a diameter of 17.6 to 27.7 mm, in males the diameter was from 17.6 to 27.7 mm and females diameter ranging from 21.1 to 25.2. The length of the descending thoracic aorta was from 18.40 to 19.41 cm.

scholarly journals ELECTRON MICROSCOPIC EXAMINATION OF THE SITES OF NUCLEAR RNA SYNTHESIS DURING AMPHIBIAN EMBRYOGENESIS

1965 ◽  
Vol 26 (3) ◽  
pp. 937-958 ◽  
Author(s):  
Shuichi Karasaki
Keyword(s):  
Rna Synthesis ◽  
Developmental Stages ◽  
Early Embryo ◽  
Tail Bud ◽  
Electron Microscopic ◽  
Electron Microscopic Autoradiography ◽  
Nuclear Rna Synthesis ◽  
Nuclear Rna ◽  
Chromatin Material ◽  
Labeled Rna

The site of H3-uridine incorporation and the fate of labeled RNA during early embryo-genesis of the newt Triturus pyrrhogaster were studied with electron microscopic autoradiography. Isolated ectodermal and mesodermal tissues from the embryos were treated in H3-uridine for 3 hours and cultured in cold solution for various periods before fixation with OsO4 and embedding in Epon. At the blastula stage, the only structural component of the nucleus seen in electron micrographs is a mass of chromatin fibrils. At the early gastrula stage, the primary nucleoli originate as small dense fibrous bodies within the chromatin material. These dense fibrous nucleoli enlarge during successive developmental stages by the acquisition of granular components 150 A in diameter, which form a layer around them. Simultaneously larger granules (300 to 500 A) appear in the chromatin, and they fill the interchromatin spaces by the tail bud stage. Autoradiographic examination has demonstrated that nuclear RNA synthesis takes place in both the nucleolus and the chromatin, with the former consistently showing more label per unit area than the latter. When changes in the distribution pattern of radioactivity were studied 3 to 24 hours after immersion in isotope at each developmental stage, the following results were obtained. Labeled RNA is first localized in the fibrous region of the nucleolus and in the peripheral region of chromatin material. After longer culture in non-radioactive medium, labeled materials also appear in the granular region of the nucleolus and in the interchromatin areas. Further incubation gives labeling in cytoplasm.

Patterning the ascidian nervous system: structure, expression and transgenic analysis of the CiHox3 gene

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4737-4748 ◽  
Author(s):  
A. Locascio ◽  
F. Aniello ◽  
A. Amoroso ◽  
M. Manzanares ◽  
R. Krumlauf ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hox Genes ◽  
Regional Identity ◽  
Regulatory Elements ◽  
System Structure ◽  
Anteroposterior Patterning ◽  
Hox Gene ◽  
The Central Nervous System ◽  
Group 3

Hox genes play a fundamental role in the establishment of chordate body plan, especially in the anteroposterior patterning of the nervous system. Particularly interesting are the anterior groups of Hox genes (Hox1-Hox4) since their expression is coupled to the control of regional identity in the anterior regions of the nervous system, where the highest structural diversity is observed. Ascidians, among chordates, are considered a good model to investigate evolution of Hox gene, organisation, regulation and function. We report here the cloning and the expression pattern of CiHox3, a Ciona intestinalis anterior Hox gene homologous to the paralogy group 3 genes. In situ hybridization at the larva stage revealed that CiHox3 expression was restricted to the visceral ganglion of the central nervous system. The presence of a sharp posterior boundary and the absence of transcript in mesodermal tissues are distinctive features of CiHox3 expression when compared to the paralogy group 3 in other chordates. We have investigated the regulatory elements underlying CiHox3 neural-specific expression and, using transgenic analysis, we were able to isolate an 80 bp enhancer responsible of CiHox3 activation in the central nervous system (CNS). A comparative study between mouse and Ciona Hox3 promoters demonstrated that divergent mechanisms are involved in the regulation of these genes in vertebrates and ascidians.

Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 759-769 ◽  
Author(s):  
M. Manzanares ◽  
S. Cordes ◽  
L. Ariza-McNaughton ◽  
V. Sadl ◽  
K. Maruthainar ◽  
...  
Keyword(s):  
Binding Sites ◽  
Hox Genes ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Enhancer Activity ◽  
Anteroposterior Patterning ◽  
Endogenous Gene ◽  
Transgenic Embryos ◽  
The Individual ◽  
Segmental Expression

During anteroposterior patterning of the developing hindbrain, the anterior expression of 3′ Hox genes maps to distinct rhombomeric boundaries and, in many cases, is upregulated in specific segments. Paralogous genes frequently have similar anterior boundaries of expression but it is not known if these are controlled by common mechanisms. The expression of the paralogous Hoxa3 and Hoxb3 genes extends from the posterior spinal cord up to the rhombomere (r) 4/5 boundary and both genes are upregulated specifically in r5. However, in this study, we have found that Hoxa3 expression is also upregulated in r6, showing that there are differences in segmental expression between paralogues. We have used transgenic analysis to investigate the mechanisms underlying the pattern of segmental expression of Hoxa3. We found that the intergenic region between Hoxa3 and Hoxa4 contains several enhancers, which summed together mediate a pattern of expression closely resembling that of the endogenous Hoxa3 gene. One enhancer specifically directs expression in r5 and r6, in a manner that reflects the upregulation of the endogenous gene in these segments. Deletion analysis localized this activity to a 600 bp fragment that was found to contain a single high-affinity binding site for the Maf bZIP protein Krml1, encoded by the kreisler gene. This site is necessary for enhancer activity and when multimerized it is sufficient to direct a kreisler-like pattern in transgenic embryos. Furthermore the r5/r6 enhancer activity is dependent upon endogenous kreisler and is activated by ectopic kreisler expression. This demonstrates that Hoxa3, along with its paralog Hoxb3, is a direct target of kreisler in the mouse hindbrain. Comparisons between the Krml1-binding sites in the Hoxa3 and Hoxb3 enhancers reveal that there are differences in both the number of binding sites and way that kreisler activity is integrated and restricted by these two control regions. Analysis of the individual sites revealed that they have different requirements for mediating r5/r6 and dorsal roof plate expression. Therefore, the restriction of Hoxb3 to r5 and Hoxa3 to r5 and r6, together with expression patterns of Hoxb3 in other vertebrate species suggests that these regulatory elements have a common origin but have later diverged during vertebrate evolution.

scholarly journals Epha1 is a cell surface marker for neuromesodermal progenitors and their early mesoderm derivatives

2019 ◽  
Author(s):  
Luisa de Lemos ◽  
André Dias ◽  
Ana Nóvoa ◽  
Moisés Mallo
Keyword(s):  
Cell Surface ◽  
Transcriptional Profiling ◽  
Surface Marker ◽  
Cell Surface Marker ◽  
Paraxial Mesoderm ◽  
Molecular Signature ◽  
Tail Bud ◽  
Molecular Fingerprint ◽  
Simple Method ◽  
Cell Subpopulations

ABSTRACTThe vertebrate body is built during embryonic development by the sequential addition of new tissue as the embryo grows at its caudal end. During this process, the neuro-mesodermal progenitors (NMPs) generate the postcranial neural tube and paraxial mesoderm. Recently, several approaches have been designed to determine their molecular fingerprint but a simple method to isolate NMPs from embryos without the need for transgenic markers is still missing. We isolated NMPs using a genetic strategy that exploits their self-renew properties, and searched their transcriptome for cell surface markers. We found a distinct Epha1 expression profile in progenitor-containing areas of the mouse embryo, consisting of two cell subpopulations with different Epha1 expression levels. We show that Sox2+/T+ cells are preferentially associated with the Epha1 compartment, indicating that NMPs might be contained within this cell pool. Transcriptional profiling showed enrichment of high Epha1-expressing cells in known NMP and early mesoderm markers. Also, tail bud cells with lower Epha1 levels contained a molecular signature suggesting the presence of notochord progenitors. Our results thus indicate that Epha1 could represent a valuable cell surface marker for different subsets of axial progenitors, most particularly for NMPs taking mesodermal fates.

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