Overexpression of the forebrain-specific homeobox gene six3 induces rostral forebrain enlargement in zebrafish

Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2973-2982 ◽  
Author(s):  
M. Kobayashi ◽  
R. Toyama ◽  
H. Takeda ◽  
I.B. Dawid ◽  
K. Kawakami
Keyword(s):  
Homeobox Gene ◽  
Cloning And Expression ◽  
Optic Stalk ◽  
Sine Oculis ◽  
Murine Homolog ◽  
Enhanced Expression ◽  
Rostral Region ◽  
The Brain ◽  
Early Gastrula ◽  
Anterior Neural Plate

The Drosophila homeobox gene sine oculis is expressed in the rostral region of the embryo in early development and is essential for eye and brain formation. Its murine homolog, Six3, is expressed in the anterior neural plate and eye anlage, and may have crucial functions in eye and brain development. In this study, we describe the cloning and expression of zebrafish six3, the apparent ortholog of the mouse Six3 gene. Zebrafish six3 transcripts are first seen in hypoblast cells in early gastrula embryos and are found in the anterior axial mesendoderm through gastrulation. six3 expression in the head ectoderm begins at late gastrula. Throughout the segmentation period, six3 is expressed in the rostral region of the prospective forebrain. Overexpression of six3 in zebrafish embryos induced enlargement of the rostral forebrain, enhanced expression of pax2 in the optic stalk and led to a general disorganization of the brain. Disruption of either the Six domain or the homeodomain abolish these effects, implying that these domains are essential for six3 gene function. Our results suggest that the vertebrate Six3 genes are involved in the formation of the rostral forebrain.

Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 845-856 ◽  
Author(s):  
M. Rhinn ◽  
A. Dierich ◽  
W. Shawlot ◽  
R.R. Behringer ◽  
M. Le Meur ◽  
...  
Keyword(s):  
Es Cells ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Regulatory Genes ◽  
Neural Function ◽  
Visceral Endoderm ◽  
Essential Function ◽  
The Brain ◽  
Anterior Neural Plate ◽  
Recombination Assay

The homeobox gene Otx2 is a mouse cognate of the Drosophila orthodenticle gene, which is required for development of the brain, rostral to rhombomere three. We have investigated the mechanisms involved in this neural function and specifically the requirement for Otx2 in the visceral endoderm and the neuroectoderm using chimeric analysis in mice and explant recombination assay. Analyses of chimeric embryos composed of more than 90% of Otx2−/− ES cells identified an essential function for Otx2 in the visceral endoderm for induction of the forebrain and midbrain. The chimeric studies also demonstrated that an anterior neural plate can form without expressing Otx2. However, in the absence of Otx2, expression of important regulatory genes, such as Hesx1/Rpx, Six3, Pax2, Wnt1 and En, fail to be initiated or maintained in the neural plate. Using explant-recombination assay, we could further demonstrate that Otx2 is required in the neuroectodem for expression of En. Altogether, these results demonstrate that Otx2 is first required in the visceral endoderm for the induction, and subsequently in the neuroectoderm for the specification of forebrain and midbrain territories.

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.

scholarly journals The Murine Neuronal Receptor NgR1 Is Dispensable for Reovirus Pathogenesis

2021 ◽  
Author(s):  
Pavithra Aravamudhan ◽  
Camila Guzman-Cardozo ◽  
Kelly Urbanek ◽  
Olivia Welsh ◽  
Jennifer Konopka-Anstadt ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Target Cells ◽  
Viral Attachment ◽  
Genetic Ablation ◽  
Murine Homolog ◽  
Intramuscular Inoculation ◽  
Neural Tissues ◽  
Mammalian Orthoreovirus ◽  
The Brain

Engagement of host receptors is essential for viruses to enter target cells and initiate infection. Expression patterns of receptors in turn dictate host and tissue tropism and disease pathogenesis during infection. Mammalian orthoreovirus (reovirus) displays serotype-dependent patterns of tropism in the murine central nervous system (CNS) that are dictated by viral attachment protein σ1. However, the receptor that mediates reovirus CNS tropism is unknown. Two proteinaceous receptors have been identified for reovirus, junctional adhesion molecule-A (JAM-A) and Nogo 66 receptor 1 (NgR1). Engagement of JAM-A is required for reovirus hematogenous dissemination but is dispensable for neural spread. To determine whether NgR1 functions in reovirus neuropathogenesis, we compared virus replication and disease following inoculation of wild-type (WT) and NgR1-/- mice. Genetic ablation of NgR1 did not alter replication of neurotropic reovirus strain T3SA- in the intestine and transmission to the brain following peroral inoculation. Viral titers in neural tissues following intramuscular inoculation, which provides access to neural dissemination routes, also were comparable in WT and NgR1-/- mice, suggesting that NgR1 is dispensable for reovirus neural spread to the CNS. The absence of both NgR1 and JAM-A also did not alter replication, neural tropism, and virulence of T3SA- following direct intracranial inoculation. In agreement with these findings, we found that the human but not the murine homolog of NgR1 functions as a receptor and confers efficient reovirus binding and infection of nonsusceptible cells in vitro. These results eliminate functions for JAM-A and NgR1 in shaping CNS tropism in mice and suggest that other receptors, yet to be identified, support this function.

A novel Xenopus mix-like gene milk involved in the control of the endomesodermal fates

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2577-2585 ◽  
Author(s):  
V. Ecochard ◽  
C. Cayrol ◽  
S. Rey ◽  
F. Foulquier ◽  
D. Caillol ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Early Response ◽  
Response Gene ◽  
Mesodermal Cell ◽  
Early Response Gene ◽  
Mesoderm Formation ◽  
Definition Of ◽  
Early Gastrula

Here we describe a novel Xenopus homeobox gene, milk, related by sequence homology and expression pattern to the vegetally expressed Mix.1. As is the case with Mix.1, milk is an immediate early response gene to the mesoderm inducer activin. milk is expressed at the early gastrula stage in the vegetal cells, fated to form endoderm, and in the marginal zone fated to form mesoderm. During gastrulation, expression of milk becomes progressively reduced in the involuting mesodermal cells but is retained in the endoderm, suggesting that it may play a key role in the definition of the endo-mesodermal boundary in the embryo. Overexpression of milk in the marginal zone blocks mesodermal cell involution, represses the expression of several mesodermal genes such as Xbra, goosecoid, Xvent-1 or Xpo and increases the expression of the endodermal gene, endodermin. In the dorsal marginal zone, overexpression of milk leads to a severe late phenotype including the absence of axial structures. Ectopic expression of milk in the animal hemisphere or in ectodermal explants induces a strong expression of endodermin. Taken together, we propose that milk plays a role in the correct patterning of the embryo by repressing mesoderm formation and promoting endoderm identity.

Competition and position-dependent targeting in the development of the Drosophila R7 visual projections

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1537-1547 ◽  
Author(s):  
J.A. Ashley ◽  
F.N. Katz
Keyword(s):  
Genetic Model ◽  
Competitive Interactions ◽  
Sine Oculis ◽  
Functional Connections ◽  
Eye Field ◽  
Target Regulation ◽  
Set Up ◽  
Molecular Bases ◽  
The Brain ◽  
Retinotopic Map

The R7 photoreceptor neuron projections form a retinotopic map in the medulla of the Drosophila optic lobe. The more inner photoreceptors mutation, an allele of gap1, results in the differentiation of excess R7s in the eye, whose axons invade the brain and establish functional connections. We have used this hyperinnervation phenotype to explore the roles of photoreceptor-target regulation, competitive interactions, and chemoaffinity in map formation. We show that the extra axons are supported in a wild-type brain, with all R7s from a single ommatidium sharing a single termination site, and thus there is no evidence that the target regulates the size of the presynaptic population. In mosaic eyes, in which ommatidia containing extra R7s are surrounded by ommatidia lacking all R7 cells, R7 axons still target to appropriate retinotopic locations in a largely empty R7 terminal field. Axons at the edges of the projection, however, send collaterals into vacant areas of the field, suggesting they are normally restrained to share single termination sites by competitive interactions. In contrast, no sprouts are seen when the vacant sites are juxtaposed with singly innervated sites. In the third instar, R7 and R8 axons transiently display halos of filopodia that overlap adjacent terminals and provide a means to assess occupancy at adjacent sites. Finally, in sine oculis larvae in which only a small number of ommatidia develop, the R7/R8 axons target to predicted dorsoventral portions of the medulla despite the absence of their neighbors, suggesting that position in the eye field determines their connectivity in the brain. We suggest that the mechanisms used to set up this insect map are formally similar to strategies used by vertebrates. The availability of a genetic model for these events should facilitate studies aimed at understanding the molecular bases of retinotopic map development.

scholarly journals Cloning and Expression of the Human Kv4.3 Potassium Channel

1999 ◽  
Vol 81 (4) ◽  
pp. 1974-1977 ◽  
Author(s):  
Daniel Dilks ◽  
Huai-Ping Ling ◽  
Mark Cockett ◽  
Patricia Sokol ◽  
Randy Numann
Keyword(s):  
Potassium Channel ◽  
Cloning And Expression ◽  
Short Version ◽  
Rt Pcr ◽  
Amino Acid Deletion ◽  
Inactivation Curve ◽  
Recovery From Inactivation ◽  
Window Current ◽  
Kinetics Of ◽  
The Brain

Cloning and expression of the human Kv4.3 potassium channel. We report on the cloning and expression of hKv4.3, a fast inactivating, transient, A-type potassium channel found in both heart and brain that is 91% homologous to the rat Kv4.3 channel. Two isoforms of hKv4.3 were cloned. One is full length (hKv4.3 long), and the other has a 19 amino acid deletion (hKv4.3 short). RT-PCR shows that the brain contains both forms of the channel RNA, whereas the heart predominantly has the longer version. Both versions of the channel were expressed in Xenopus oocytes, and both contain a significant window or noninactivating current seen near potentials of −30 to −40 mV. The inactivation curve for hKv4.3 short is shifted 10 mV positive relative to hKv4.3 long. This causes the peak window current for the short version to occur near −30 mV and the peak for the longer version to be at −40 mV. There was little difference in the recovery from inactivation or in the kinetics of inactivation between the two isoforms of the channel.

X-Linked Lissencephaly With Abnormal Genitalia as a Tangential Migration Disorder Causing Intractable Epilepsy: Proposal for a New Term, “Interneuronopathy”

2004 ◽  
Vol 19 (3) ◽  
pp. 392-397
Author(s):  
Mitsuhiro Kato ◽  
William B. Dobyns
Keyword(s):  
Intractable Epilepsy ◽  
Brain Magnetic Resonance Imaging ◽  
Homeobox Gene ◽  
Tangential Migration ◽  
Intractable Seizures ◽  
Migration Disorder ◽  
Male Patients ◽  
Paired Class ◽  
Clonic Convulsions ◽  
The Brain

X-linked lissencephaly with abnormal genitalia is the first human disorder in which deficient tangential migration in the brain has been demonstrated. Male patients with X-linked lissencephaly with abnormal genitalia show intractable seizures, especially clonic convulsions or myoclonus from the first day of life, but neither infantile spasms nor hypsarrhythmia on electroencephalograms so far. Brain magnetic resonance imaging shows anterior pachygyria and posterior agyria with a mildly thick cortex, agenesis of the corpus callosum, and dysplastic basal ganglia. ARX, a paired-class homeobox gene with four polyalanine sequences, is a responsible gene for X-linked lissencephaly with abnormal genitalia. The brain of Arx knockout mice shows aberrant tangential migration and differentiation of γ-aminobutyric acid (GABA)ergic interneurons. In human X-linked lissencephaly with abnormal genitalia, a neuropathologic study has suggested a loss of interneurons. Meanwhile, polyalanine expansion of ARX causes symptomatic or nonsymptomatic West's syndrome and nonsyndromic mental retardation. The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations is considered to be caused by a disorder of interneurons involving a tangential migration disorder. We propose “interneuronopathy” as a term for this. ( J Child Neurol 2005;20:392—397).

scholarly journals cDNA cloning and expression of rat homeobox gene, Hex, and functional characterization of the protein

1999 ◽  
Vol 339 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Takashi TANAKA ◽  
Tetsuya INAZU ◽  
Kazuya YAMADA ◽  
Zaw MYINT ◽  
Vincent W. KENG ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Rat Liver ◽  
Functional Characterization ◽  
Homeobox Gene ◽  
Hepatoma Cells ◽  
Cloning And Expression ◽  
Expression Vectors ◽  
Luciferase Reporter ◽  
Cdna Clones

We isolated two cDNA clones of rat Hex, a homeobox protein, studied its expression in rat liver and various cells, and characterized the protein. The levels of Hex mRNA were only slightly increased in liver of rats refed with a high-carbohydrate diet or after partial hepatectomy. Whereas the expression of Hex mRNA was detected in hepatocytes isolated from adult rat liver and also in highly differentiated hepatoma cells, no Hex mRNA was detected in poorly differentiated hepatoma cells. Hex mRNA was also detected in liver from embryo aged 15 days. Expression of Hex was increased in F9 cells during differentiation into visceral endoderm cells by treatment with retinoic acid. This stimulation occurred prior to an increase in the level of α-fetoprotein mRNA. When fusion-protein expression vectors of GAL4 DNA-binding domain and Hex were co-transfected with luciferase reporter plasmid, with or without five copies of the GAL4-binding site, into HepG2 cells, the luciferase activities were decreased in concentration- and GAL4-binding site-dependent manners. This repression did not require the presence of the homeodomain, which is located between the amino acid residues 137 and 196. Its repression domain was mapped between the residues 45 and 136 in the proline-rich N-terminal region. In addition, the homeodomain was responsible for DNA-binding of Hex. These results indicate that Hex functions as a transcriptional repressor and may be involved in the differentiation and/or maintenance of the differentiated state in hepatocytes.

scholarly journals Enhanced Expression of Markers for Astrocytes in the Brain of a Line of GFAP-TK Transgenic Mice

2017 ◽  
Vol 11 ◽  
Author(s):  
Xiaoqin Zhang ◽  
Dongpi Wang ◽  
Hongyu Pan ◽  
Binggui Sun
Keyword(s):  
Transgenic Mice ◽  
Enhanced Expression ◽  
The Brain

scholarly journals Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed in the anterior embryonic shield and the developing eye

1998 ◽  
Vol 74 (1-2) ◽  
pp. 159-164 ◽  
Author(s):  
Felix Loosli ◽  
Reinhard W. Köster ◽  
Matthias Carl ◽  
Annette Krone ◽  
Joachim Wittbrodt
Keyword(s):  
Homeobox Gene ◽  
Sine Oculis ◽  
Embryonic Shield
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