Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2923-2934 ◽  
Author(s):  
K.M. Wassarman ◽  
M. Lewandoski ◽  
K. Campbell ◽  
A.L. Joyner ◽  
J.L. Rubenstein ◽  
...  
Keyword(s):  
Normal Development ◽  
Motor Nerve ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Mouse Embryos ◽  
Loss Of Function ◽  
Isthmic Nuclei ◽  
Signaling Center ◽  
Derivatives Of ◽  
Anterior Posterior

Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate stage for the correct specification and normal proliferation or survival of anterior hindbrain precursors. It is also required to maintain normal patterns of expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode signaling molecules thought to be key components of the mid/hindbrain (isthmic) organizer. In the absence of Gbx2 function, isthmic nuclei, the cerebellum, motor nerve V, and other derivatives of rhombomeres 1–3 fail to form. Additionally, the posterior midbrain in the mutant embryos appears to be extended caudally and displays abnormalities in anterior/posterior patterning. The failure of anterior hindbrain development is presumably due to the loss of Gbx2 function in the precursors of the anterior hindbrain. However, since Gbx2 expression is not detected in the midbrain it seems likely that the defects in midbrain anterior/posterior patterning result from an abnormal isthmic signaling center. These data provide genetic evidence for a link between patterning of the anterior hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2 as a gene required for these processes to occur normally.

scholarly journals Role of Xrx1 in Xenopus eye and anterior brain development

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2451-2460 ◽  
Author(s):  
M. Andreazzoli ◽  
G. Gestri ◽  
D. Angeloni ◽  
E. Menna ◽  
G. Barsacchi
Keyword(s):  
Brain Development ◽  
Transcriptional Activation ◽  
Homeobox Gene ◽  
Brain Regions ◽  
Neural Plate ◽  
Loss Of Function ◽  
Expression Domain ◽  
Severe Impairment ◽  
Development Analysis ◽  
Anterior Neural Plate

The anteriormost part of the neural plate is fated to give rise to the retina and anterior brain regions. In Xenopus, this territory is initially included within the expression domain of the bicoid-class homeobox gene Xotx2 but very soon, at the beginning of neurulation, it becomes devoid of Xotx2 transcripts in spatiotemporal concomitance with the transcriptional activation of the paired-like homeobox gene Xrx1. By use of gain- and loss-of-function approaches, we have studied the role played by Xrx1 in the anterior neural plate and its interactions with other anterior homeobox genes. We find that, at early neurula stage Xrx1 is able to repress Xotx2 expression, thus first defining the retina-diencephalon territory in the anterior neural plate. Overexpression studies indicate that Xrx1 possesses a proliferative activity that is coupled with the specification of anterior fate. Expression of a Xrx1 dominant repressor construct (Xrx1-EnR) results in a severe impairment of eye and anterior brain development. Analysis of several brain markers in early Xrx1-EnR-injected embryos reveals that anterior deletions are preceded by a reduction of anterior gene expression domains in the neural plate. Accordingly, expression of anterior markers is abolished or decreased in animal caps coinjected with the neural inducer chordin and the Xrx1-EnR construct. The lack of expansion of mid-hindbrain markers, and the increase of apoptosis in the anterior neural plate after Xrx1-EnR injection, indicate that anterior deletions result from an early loss of anterior neural plate territories rather than posteriorization of the neuroectoderm. Altogether, these data suggest that Xrx1 plays a role in assigning anterior and proliferative properties to the rostralmost part of the neural plate, thus being required for eye and anterior brain development.

Localization of Intracisternal a Particle Antigens in Neoplastic Cells and Preimplantation Mouse Embryos

1980 ◽  
Vol 38 ◽  
pp. 696-697
Author(s):  
Thomas T.F. Huang ◽  
Patricia G. Calarco
Keyword(s):  
Endoplasmic Reticulum ◽  
Normal Development ◽  
Mouse Embryos ◽  
Neoplastic Cells ◽  
Large Numbers ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Intracisternal A Particle ◽  
Normal Feature

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.

Anterior mesendoderm induces mouse Engrailed genes in explant cultures

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 139-149 ◽  
Author(s):  
S.L. Ang ◽  
J. Rossant
Keyword(s):  
Direct Evidence ◽  
Neural Tissue ◽  
Explant Culture ◽  
Neural Plate ◽  
Explant Cultures ◽  
Neural Marker ◽  
Engrailed Genes ◽  
Anterior Posterior

We have developed germ layer explant culture assays to study the role of mesoderm in anterior-posterior (A-P) patterning of the mouse neural plate. Using isolated explants of ectodermal tissue alone, we have demonstrated that the expression of Engrailed-1 (En-1) and En-2 genes in ectoderm is independent of mesoderm by the mid- to late streak stage, at least 12 hours before their onset of expression in the neural tube in vivo at the early somite stage. In recombination explants, anterior mesendoderm from headfold stage embryos induces the expression of En-1 and En-2 in pre- to early streak ectoderm and in posterior ectoderm from headfold stage embryos. In contrast, posterior mesendoderm from embryos of the same stage does not induce En genes in pre- to early streak ectoderm but is able to induce expression of a general neural marker, neurofilament 160 × 10(3) M(r). These results provide the first direct evidence for a role of mesendoderm in induction and regionalization of neural tissue in mouse.

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.

A developmental pathway controlling outgrowth of the Xenopus tail bud

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1611-1620 ◽  
Author(s):  
C.W. Beck ◽  
J.M. Slack
Keyword(s):  
Normal Development ◽  
Posterior Part ◽  
Neural Plate ◽  
General Mechanism ◽  
Developmental Pathway ◽  
Tail Bud ◽  
Neural Tubes ◽  
Tailbud Stage ◽  
Tail Tip ◽  
Host Embryo

We have developed a new assay to identify factors promoting formation and outgrowth of the tail bud. A piece of animal cap filled with the test mRNAs is grafted into the posterior region of the neural plate of a host embryo. With this assay we show that expression of a constitutively active Notch (Notch ICD) in the posterior neural plate is sufficient to produce an ectopic tail consisting of neural tube and fin. The ectopic tails express the evenskipped homologue Xhox3, a marker for the distal tail tip. Xhox3 will also induce formation of an ectopic tail in our assay. We show that an antimorphic version of Xhox3, Xhox3VP16, will prevent tail formation by Notch ICD, showing that Xhox3 is downstream of Notch signalling. An inducible version of this reagent, Xhox3VP16GR, specifically blocks tail formation when induced in tailbud stage embryos, comfirming the importance of Xhox3 for tail bud outgrowth in normal development. Grafts containing Notch ICD will only form tails if placed in the posterior part of the neural plate. However, if Xwnt3a is also present in the grafts they can form tails at any anteroposterior level. Since Xwnt3a expression is localised appropriately in the posterior at the time of tail bud formation it is likely to be responsible for restricting tail forming competence to the posterior neural plate in our assay. Combined expression of Xwnt3a and active Notch in animal cap explants is sufficient to induce Xhox3, provoke elongation and form neural tubes. Conservation of gene expression in the tail bud of other vertebrates suggests that this pathway may describe a general mechanism controlling tail outgrowth and secondary neurulation.

Mechanism of anteroposterior axis specification in vertebrates. Lessons from the amphibians

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 285-302 ◽  
Author(s):  
J.M. Slack ◽  
D. Tannahill
Keyword(s):  
Molecular Markers ◽  
Expression Patterns ◽  
Signal Transduction Pathway ◽  
Homeobox Gene ◽  
Neural Induction ◽  
High Sensitivity ◽  
Neural Plate ◽  
Mesoderm Induction ◽  
Inducing Factors ◽  
Almost All

Interest in the problem of anteroposterior specification has quickened because of our near understanding of the mechanism in Drosophila and because of the homology of Antennapedia-like homeobox gene expression patterns in Drosophila and vertebrates. But vertebrates differ from Drosophila because of morphogenetic movements and interactions between tissue layers, both intimately associated with anteroposterior specification. The purpose of this article is to review classical findings and to enquire how far these have been confirmed, refuted or extended by modern work. The “pre-molecular” work suggests that there are several steps to the process: (i) Formation of anteroposterior pattern in mesoderm during gastrulation with posterior dominance. (ii) Regional specific induction of ectoderm to form neural plate. (iii) Reciprocal interactions from neural plate to mesoderm. (iv) Interactions within neural plate with posterior dominance. Unfortunately, almost all the observable markers are in the CNS rather than in the mesoderm where the initial specification is thought to occur. This has meant that the specification of the mesoderm has been assayed indirectly by transplantation methods such as the Einsteckung. New molecular markers now supplement morphological ones but they are still mainly in the CNS and not the mesoderm. A particular interest attaches to the genes of the Antp-like HOX clusters since these may not only be markers but actual coding factors for anteroposterior levels. We have a new understanding of mesoderm induction based on the discovery of activins and fibroblast growth factors (FGFs) as candidate inducing factors. These factors have later consequences for anteroposterior pattern with activin tending to induce anterior, and FGF posterior structures. Recent work on neural induction has implicated cAMP and protein kinase C (PKC) as elements of the signal transduction pathway and has provided new evidence for the importance of tangential neural induction. The regional specificity of neural induction has been reinvestigated using molecular markers and provides conclusions rather similar to the classical work. Defects in the axial pattern may be produced by retinoic acid but it remains unclear whether its effects are truly coordinate ones or are concentrated in certain regions of high sensitivity. In general the molecular studies have supported and reinforced the “pre-molecular ones”. Important questions still remain: (i) How much pattern is there in the mesoderm (how many states?) (ii) How is this pattern generated by the invaginating organizer? (iii) Is there one-to-one transmission of codings to the neural plate? (iv) What is the nature of the interactions within the neural plate? (v) Are the HOX cluster genes really the anteroposterior codings?

A study of the properties, morphogenetic potencies and prospective fate of outer and inner layers of ectodermal and chordamesodermal regions during gastrulation, in various Anuran amphibians

Development ◽  
1983 ◽  
Vol 75 (1) ◽  
pp. 67-86
Author(s):  
T. A. Dettlaff
Keyword(s):  
Outer Layer ◽  
Normal Development ◽  
Neural Plate ◽  
Ependymal Cells ◽  
Epithelial Layer ◽  
Bombina Bombina ◽  
Cell Layers ◽  
The Brain ◽  
Early Gastrula

In both the ectodermal and the chordamesodermal regions of Anuran embryos, the outer layer of cells possesses epithelial properties and has the same restricted morphogenetic potencies. It is thus interchangeable between the regions, capable of epiboly and, when underlain by notochord material, of the formation of bottle-shaped cells as at the blastoporal groove, and invagination. When taken from the chordamesoderm region, this outer layer has no inducing effect on the ectoderm of the early gastrula. In normal development the outer layer of the neural plate takes an active part in forming the neural tube cavity. It gives rise to the neuroepithelial roof of the diencephalon and medulla oblongata and, when underlain by neuroblasts that develop from the inner cell layers, to ependymal cells of the brain wall. The outer layer of the notochord material is included in the epithelial layer underlying the roof of the gastrocoel - the hypochordal plate. The inner layers of these regions consist of loosely arranged cells and normally have no epithelial properties although, when taken from the ectoderm region, they may acquire such properties upon long-term contact with the environment. However they have wide morphogenetic potencies; the differences in these potencies between cells taken from the various presumptive regions being less than the differences between outer and inner cell layers in each region. Maps are provided which show the arrangement of presumptive rudiments in the ectoderm and chordamesoderm on sagittal sections through Bombina bombina embryos in early and late gastrulation.

FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain

Development ◽  
2002 ◽  
Vol 129 (16) ◽  
pp. 3825-3837 ◽  
Author(s):  
Lisa Maves ◽  
William Jackman ◽  
Charles B. Kimmel
Keyword(s):  
Neuronal Differentiation ◽  
Crucial Role ◽  
Time Lapse ◽  
Signaling Molecules ◽  
Neural Plate ◽  
Fgf Signaling ◽  
Genetic Mosaic ◽  
Signaling Center ◽  
Signaling Activity ◽  
Rhombomere 4

The segmentation of the vertebrate hindbrain into rhombomeres is highly conserved, but how early hindbrain patterning is established is not well understood. We show that rhombomere 4 (r4) functions as an early-differentiating signaling center in the zebrafish hindbrain. Time-lapse analyses of zebrafish hindbrain development show that r4 forms first and hindbrain neuronal differentiation occurs first in r4. Two signaling molecules, FGF3 and FGF8, which are both expressed early in r4, are together required for the development of rhombomeres adjacent to r4, particularly r5 and r6. Transplantation of r4 cells can induce expression of r5/r6 markers, as can misexpression of either FGF3 or FGF8. Genetic mosaic analyses also support a role for FGF signaling acting from r4. Taken together, our findings demonstrate a crucial role for FGF-mediated inter-rhombomere signaling in promoting early hindbrain patterning and underscore the significance of organizing centers in patterning the vertebrate neural plate.

scholarly journals Polyamine Homeostasis in Snyder-Robinson Syndrome

2018 ◽  
Vol 6 (4) ◽  
pp. 112 ◽  
Author(s):  
Tracy Murray-Stewart ◽  
Matthew Dunworth ◽  
Jackson Foley ◽  
Charles Schwartz ◽  
Robert Casero
Keyword(s):  
Tissue Transglutaminase ◽  
Decarboxylase Activity ◽  
Loss Of Function ◽  
Transport Activity ◽  
Spermine Synthase ◽  
Catabolic Enzymes ◽  
Polyamine Transport ◽  
Exogenous Spermine ◽  
Mutant Cells ◽  
Derivatives Of

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

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