Roles of Pax-6 in murine diencephalic development

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1573-1582 ◽  
Author(s):  
N. Warren ◽  
D.J. Price
Keyword(s):  
Gene Expression ◽  
Regional Differences ◽  
Third Ventricle ◽  
Regulatory Gene ◽  
Wild Type ◽  
Dorsal Midline ◽  
The Third ◽  
Normal Expression ◽  
In Situ Hybridizations

Pax-6 is one of the earliest regulatory genes to be expressed in the diencephalon. We tested whether normal Pax-6 protein is required for early diencephalic development by examining morphology, precursor proliferation and patterns of regulatory gene expression in the embryonic diencephalon of Small-eye mice (Pax-6 mutants). In Small-eye mice, diencephalic morphology was abnormal at all the embryonic ages studied (days 10.5, 12.5 and 14.5). Regional differences in diencephalic cell density were lost, the diencephalon/mesencephalon boundary was unclear and the third ventricle was enlarged. We estimated diencephalic proliferative rates after labelling with bromodeoxyuridine and found that they were abnormally low in mutants aged embryonic day 10.5. In older mutants, the diencephalon contained fewer cells than normal. In wild-type E14.5 diencephalon, Pax-6, Dlx-2 and Wnt-3 are expressed in discrete regions along the rostrocaudal and dorsoventral axes. In situ hybridizations for these genes in E14.5 Small-eye mice revealed discrete zones of diencephalic expression that had similar relative positions to those in wild-type mice. Some differences of detail in their expression were seen: Pax-6 had an expanded rostral domain of expression and an abnormally indistinct caudal boundary; Dlx-2 had a diffuse, rather than a sharp, caudal boundary of expression; the normally high dorsal midline expression of Wnt-3 was lost. We conclude that normal expression of Pax-6 is required for the correct regulation of diencephalic precursor proliferation. Pax-6 may also control some aspects of diencephalic differentiation, but its mutation in Small-eye mice does not preclude the development of a degree of diencephalic regionalization resembling that in normal mice.

Histology and fine structure of the pre-optic nucleus and hypothalamic tracts of the European eel Anguilla anguilla L

1969 ◽  
Vol 256 (804) ◽  
pp. 135-145 ◽  
Keyword(s):  
Electron Microscopy ◽  
Anterior Margin ◽  
Third Ventricle ◽  
Anguilla Anguilla ◽  
Structural Features ◽  
Ependymal Cells ◽  
European Eel ◽  
The Third ◽  
Secretory Products

The pre-optic nucleus and hypothalamic tracts of intact and hypophysectomized specimens of the European eel Anguilla anguilla L. have been studied in situ and by optical and electron microscopy. The in situ technique reveals a hitherto unsuspected degree of segregation of the neurosecretory axons which form up to five discrete tracts having separate origins and following distinct paths before converging, at the level of the anterior margin of the pituitary, to form a median tract. The structure of the pre-optic neurons, as revealed by several different techniques, is described and it is shown that their synthetic poles, identified by a prominent cap of endoplasmic reticulum, are precisely orientated towards the third ventricle and are separated from it by, at most, two or three layers of ependymal cells. Electron microscopy shows that the secretory products lie mainly in the axonal ends of the cells though in Bouin-fixed, wax-embedded material the entire perikaryon stains with neurosecretory dyes and this, and their proximity to the third ventricle, gives the impression that they secrete into the latter, as well as centripetally. This may well be so, but from the work described below it seems more likely that these neurons receive nutrients, or stimuli, or both, from the third ventricle. Two types of pre-optic neurons, separable by structural features as well as by the size of the elementary granules they contain have been identified; these probably give rise to two of the fibre types identified in the neurohypophysis of the eel by Knowles & Vollrath. Aggregations of neurosecretion, common in the fish pre-optic nucleus, and also, much rarer, colloid vesicles, are described and discussed.

Differential Expression of Mll-AF9 Up-Regulated Genes Correlates with Enhanced Self-Renewal of Hematopoietic Progenitors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 733-733 ◽  
Author(s):  
Ashish R. Kumar ◽  
Wendy A. Hudson ◽  
Weili Chen ◽  
Rodney A. Staggs ◽  
Anne-Francoise Lamblin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Fusion Gene ◽  
Expression Profiles ◽  
Cell Types ◽  
Third Generation ◽  
Wild Type ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
The Third

Abstract In order to understand the pathophysiology of leukemia, we need to study the effects of leukemic oncogenes on the rare hematopoietic stem and progenitor cells. We investigated the self-renewal capabilities of the various hematopoietic cell types derived from Mll-AF9 knock-in mice. We used the murine knock-in model since it offers the advantage of a single copy of the Mll-fusion gene under the control of the endogenous promoter present in every hematopoietic stem/progenitor cell. In methylcellulose cultures, we compared myeloid colony formation of Mll-AF9 cells to wild type progenitor populations over three generations of plating. In the first generation of plating, the Mll-AF9 common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) formed more colonies than the hematopoietic stem cells (HSCs) and common lymphoid progenitors (CLPs). However, at the third generation of plating, colony numbers formed by Mll-AF9 HSCs and CLPs were significantly greater than those formed by CMPs and GMPs. By the third generation only occasional colonies were found in the wild type groups. These results demonstrate that while Mll-AF9 led to an increase in self-renewal of all 4 cell types studied, these effects were more pronounced in HSCs and CLPs. To identify the downstream genes that mediate the growth deregulatory effects of Mll-AF9, we compared gene expression profiles of Mll-AF9 derived cells to their wild type counterparts. To assess gene expression levels, we extracted RNA from wild type and Mll-AF9 HSCs, CLPs, CMPs and GMPs. We then amplified and labeled the RNA for analysis by Affymetrix murine 430 2.0 genome arrays. In an unsupervised analysis, the various Mll-AF9 cells clustered with their corresponding wild type counterparts, indicating that the expression of most genes was not significantly altered by Mll-AF9. To identify the genes that are differentially expressed in the Mll-AF9 derived cells, we performed a two-way ANOVA (with the genotype and cell type as the two variables) allowing for a false discovery rate of 10%. In this analysis, we found that 76 genes were up-regulated in all Mll-AF9 progenitor cells compared to their wild-type counterparts. This list included known targets of Mll-fusion proteins Hoxa5, Hoxa7, Hoxa9 and Hoxa10. Also included were Evi1 and Mef2c, two genes that have been implicated in promoting enhanced self-renewal of murine hematopoietic cells. Importantly, in wild type mice, these 6 genes were expressed at higher levels in HSCs and CLPs compared to CMPs and GMPs (average 3–25 fold). While we observed an average 2–10 fold increase in expression of these genes in all Mll-AF9 cell types compared to their respective wild type controls, the expression level was 3–8 fold higher in Mll-AF9 HSCs and CLPs compared to CMPs and GMPs. Thus, the expression of genes known to be intrinsically related to self-renewal is further enhanced as a result of the Mll-AF9 fusion gene. In conclusion, while activation of the Mll-AF9 genetic program and the resulting enhanced self-renewal occurs in all 4 cell types studied, these effects are greatest in HSCs and CLPs. Thus, HSCs and CLPs are likely to be more efficient than CMPs and GMPs in producing cellular expansion and targets for cooperating mutations resulting in leukemia.

Cross regulation of decapentaplegic and Ultrabithorax transcription in the embryonic visceral mesoderm of Drosophila

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1211-1222 ◽  
Author(s):  
D.A. Hursh ◽  
R.W. Padgett ◽  
W.M. Gelbart
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Family Member ◽  
Reporter Gene ◽  
Expression Patterns ◽  
Reporter Genes ◽  
Regulatory Elements ◽  
Wild Type ◽  
Visceral Mesoderm ◽  
Normal Expression

The Drosophila decapentaplegic gene (dpp) encodes a TGF-beta family member involved in signal transduction during embryonic midgut formation. The shortvein (shv) class of cis-regulatory dpp mutants disrupt expression in parasegments 4 and 7 (ps4 and ps7) of the embryonic visceral mesoderm (VM) surrounding the gut and cause abnormalities in gut morphogenesis. We demonstrate that cis-regulatory elements directing expression in ps4 and ps7 are separable and identify DNA fragments that generate ps4 and ps7 expression patterns using reporter gene constructs. dpp reporter gene expression in both ps4 and ps7 is autoregulated as it requires endogenous dpp+ activity. Reporter gene ps7 expression requires the wild-type action of Ultra-bithorax (Ubx), and abdominal-A. Furthermore, the expression of certain Ubx reporter genes is coincident with dpp in the VM. Both the mis-expression of Ubx reporter genes in the developing gastric caecae at ps4 and its normal expression in ps7 are dependent upon endogenous dpp+ activity. We conclude that dpp both responds to and regulates Ubx in ps7 of the visceral mesoderm and that Ubx autoregulation within this tissue may be indirect as it requires more components than have previously been thought.

scholarly journals The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice

2006 ◽  
Vol 37 (2) ◽  
pp. 301-316 ◽  
Author(s):  
Andreas Petri ◽  
Jonas Ahnfelt-Rønne ◽  
Klaus Stensgaard Frederiksen ◽  
David George Edwards ◽  
Dennis Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
And Function ◽  
Deficient Mice

To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared to controls. Many of them were previously described to be involved in endocrine development and function. Among the genes not previously characterized were Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and the Iroquois-type homeobox gene Irx1, the latter was selected for further investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1 and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon-, but not insulin- or somatostatin-producing cells in mice and chicken. These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of α-cell-specific gene expression.

scholarly journals Mutations in SIX1 associated with Branchio-oto-renal Syndrome (BOR) differentially affect otic expression of putative target genes

2021 ◽  
Author(s):  
Tanya Mehdizadeh ◽  
Himani Datta Majumdar ◽  
Sahra Ahsan ◽  
Andre Luiz Pasqua Tavares ◽  
Sally A Moody
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Otic Vesicle ◽  
Wild Type ◽  
Single Nucleotide ◽  
Putative Target ◽  
Individual Effects ◽  
Factor Interactions ◽  
Ability To Drive

Single nucleotide mutations in SIX1 are causative in some individuals diagnosed with branchiootic/branchio-oto-renal (BOR) syndrome. To test whether these mutations have differential effects on otic gene expression, we engineered four BOR mutations in Xenopus six1 and targeted mutant protein expression to the neural crest and cranial placode precursor cells in wild-type embryos. Changes in the otic expression of putative Six1 targets and/or co-factors were monitored by qRT-PCR and in situ hybridization. We found that each mutant had a different combination of effects. The V17E mutant reduced eya2, tspan13, zbtb16 and pa2g4 otic vesicle expression at a frequency indistinguishable from wildtype Six1, but reduced prdm1 more and spry1 less compared to wild-type Six1. For most of these genes, the R110W, W122R and Y129C mutants were significantly less repressive compared to wild-type Six1. Their individual effects varied according to the level at which they were expressed. The R110W, W122R and Y129C mutants also often expanded prdm1 otic expression. Since previous studies showed that all four mutants are transcriptionally deficient and differ in their ability to interact with co-factors such as Eya1, we propose that altered co-factor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression.

scholarly journals New Target Genes Controlled by the Bradyrhizobium japonicum Two-Component Regulatory System RegSR

2007 ◽  
Vol 189 (24) ◽  
pp. 8928-8943 ◽  
Author(s):  
Andrea Lindemann ◽  
Annina Moser ◽  
Gabriella Pessi ◽  
Felix Hauser ◽  
Markus Friberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitrogen Fixation ◽  
Bradyrhizobium Japonicum ◽  
Target Genes ◽  
Regulatory Gene ◽  
Wild Type ◽  
Transcription Profiling ◽  
Two Component ◽  
Regulated Gene Expression

ABSTRACT RegSR-like proteins, members of the family of two-component regulatory systems, are present in a large number of proteobacteria in which they globally control gene expression mostly in a redox-responsive manner. The controlled target genes feature an enormous functional diversity. In Bradyrhizobium japonicum, the facultative root nodule symbiont of soybean, RegSR activate the transcription of the nitrogen fixation regulatory gene nifA, thus forming a RegSR-NifA cascade which is part of a complex regulatory network for gene regulation in response to changing oxygen concentrations. Whole-genome transcription profiling was performed here in order to assess the full regulatory scope of RegSR. The comparative analysis of wild-type and ΔregR cells grown under oxic and microoxic conditions revealed that expression of almost 250 genes is dependent on RegR, a result that underscores the important contribution of RegR to oxygen- or redox-regulated gene expression in B. japonicum. Furthermore, transcription profiling of ΔregR bacteroids compared with wild-type bacteroids revealed expression changes for about 1,200 genes in young and mature bacteroids. Incidentally, many of these were found to be induced in symbiosis when wild-type bacteroids were compared with free-living, culture-grown wild-type cells, and they appeared to encode diverse functions possibly related to symbiosis and nitrogen fixation. We demonstrated direct RegR-mediated control at promoter regions of several selected target genes by means of DNA binding experiments and in vitro transcription assays, which revealed six novel direct RegR target promoters.

scholarly journals Growth, photosynthesis, and gene expression in Chlamydomonas over a range of CO2 concentrations and CO2/O2 ratios: CO2 regulates multiple acclimation states

2005 ◽  
Vol 83 (7) ◽  
pp. 796-809 ◽  
Author(s):  
Peter Vance ◽  
Martin H Spalding
Keyword(s):  
Gene Expression ◽  
Doubling Time ◽  
Wild Type ◽  
Airlift Bioreactors ◽  
Cell Doubling Time ◽  
Glycolate Dehydrogenase ◽  
Type C ◽  
Induced Genes ◽  
Inducible Genes

Growth, photosynthesis, and induction of two low CO2-inducible genes of Chlamydomonas reinhardtii Dangeard strain CC125 were quantified in a range of physiologically relevant CO2 and O2 concentrations (5%–0.005% CO2 and 20% or 2% O2) using airlift bioreactors to facilitate the simultaneous measurement of both growth and in situ photosynthetic rates. Within these CO2 concentration ranges, O2 concentrations (20% vs. 2%) had no discernable effect on growth, photosynthetic rate, or induction of the periplasmic carbonic anhydrase (Cah1) and glycolate dehydrogenase (Gdh) genes in wild-type C. reinhardtii. These results failed to support the hypothesis that the CO2/O2 ratio plays any role in signaling for the up-regulation of limiting CO2-induced genes and (or) of the CO2-concentrating mechanism (CCM). The mRNA abundance of the Cah1 and Gdh genes appeared to be regulated in concert, suggesting co-regulation by the same signaling pathway, which, because of a lack of an O2 effect, seems unlikely to involve photorespiration or a photorespiratory metabolite. Instead, it appeared that the CO2 concentration alone was responsible for regulation of limiting CO2 acclimation responses. Based on growth, photosynthesis, and gene expression characteristics, three distinct CO2-regulated physiological states were recognized within the studied parameters, a high CO2 (5%–0.5%) state, a low CO2 (0.4%–0.03%) state, and a very low CO2 (0.01%–0.005%) state. Induction of Cah1 expression and Gdh up-regulation occurred at a CO2 concentration between 0.5% and 0.4% CO2, delineating the high from the low CO2 states. Photosynthetic characteristics also were distinct in the three CO2-regulated physiological states, e.g., the estimated K0.5(CO2) of the high CO2, low CO2, and very low CO2 states were 72, 10, and 0.9 µmol·L–1 CO2, respectively. In addition to a greater photosynthetic CO2 affinity, the very low CO2 state could be distinguished from the low CO2 state by an increased cell-doubling time and a smaller cell size.Key words: algae, Chlamydomonas, CO2, gene expression, induction, photorespiration, photosynthesis.

scholarly journals Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice

2012 ◽  
Vol 302 (11) ◽  
pp. G1336-G1342 ◽  
Author(s):  
Go Yoshimichi ◽  
Chunmin C. Lo ◽  
Kellie L. K. Tamashiro ◽  
Liyun Ma ◽  
Dana M. Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Food System ◽  
Nucleus Tractus Solitarius ◽  
Wild Type ◽  
Post Hoc Analysis ◽  
Nodose Ganglia ◽  
Post Hoc ◽  
The Brain

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

Sign in / Sign up

Export Citation Format

Share Document