A dominant mutation in the maize homeobox gene, Knotted-1, causes its ectopic expression in leaf cells with altered fates

Development ◽  
1992 ◽  
Vol 116 (1) ◽  
pp. 21-30 ◽  
Author(s):  
L.G. Smith ◽  
B. Greene ◽  
B. Veit ◽  
S. Hake
Keyword(s):  
Leaf Development ◽  
Early Stage ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Vascular Bundles ◽  
Ground Tissue ◽  
Wild Type ◽  
Dominant Mutation ◽  
Coding Regions ◽  
Undifferentiated Cells

Dominant mutations of the Knotted-1 (Kn1) homeobox gene of maize alter the differentiation and growth of cells associated with leaf veins. By analyzing Kn1 transcripts and KN1 protein, we show that the gene is not expressed at high levels during the development of wild-type leaves. Instead, Kn1 is expressed in apical meristems of vegetative and floral shoots, and is downregulated as leaves and floral organs are initiated. Kn1 is also expressed in relatively undifferentiated cells within developing vascular bundles, as well as ground tissue, in immature, unelongated axes of wild-type vegetative and floral shoots. In Kn1-N2 mutant plants, quantitative, but not qualitative differences are apparent in Kn1 transcripts and KN1 protein, consistent with previous observations that dominant Kn1 mutations map to non-coding regions of the gene. Kn1 is expressed ectopically in vascular bundles within developing mutant leaves in a pattern that correlates with the phenotypic alterations produced by the Kn1-N2 mutation. Thus, Kn1 apparently alters the fates of leaf cells in which it is ectopically expressed from an early stage of leaf development. Based on these observations, we hypothesize that Kn1 functions in its wild-type context as a regulator of cell determination.

Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4303-4313 ◽  
Author(s):  
W. Liao ◽  
C.Y. Ho ◽  
Y.L. Yan ◽  
J. Postlethwait ◽  
D.Y. Stainier
Keyword(s):  
Transcription Factor ◽  
Blood Cells ◽  
Early Stage ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Transcription Factor Gene ◽  
Factor Gene ◽  
Molecular Events ◽  
Initial Framework

During embryogenesis, endothelial and blood precursors are hypothesized to arise from a common progenitor, the hemangioblast. Several genes that affect the differentiation of, or are expressed early in, both the endothelial and blood lineages may in fact function at the level of the hemangioblast. For example, the zebrafish cloche mutation disrupts the differentiation of both endothelial and blood cells. The transcription factor gene scl is expressed in both endothelial and blood lineages from an early stage and can regulate their differentiation. Here we report that in zebrafish the homeobox gene hhex (previously called hex) is also expressed in endothelial and blood lineages from an early stage. We find that hhex expression in these lineages is significantly reduced in cloche mutant embryos, indicating that hhex functions downstream of cloche to regulate endothelial and blood differentiation. Ectopic expression of hhex through injection of a DNA construct leads to the premature and ectopic expression of early endothelial and blood differentiation genes such as fli1, flk1 and gata1, indicating that Hhex can positively regulate endothelial and blood differentiation. However, analysis of a hhex deficiency allele shows that hhex is not essential for early endothelial and blood differentiation, suggesting that another gene, perhaps scl, compensates for the absence of Hhex function. Furthermore, we find that hhex and scl can induce each other's expression, suggesting that these two genes cross-regulate each other during early endothelial and blood differentiation. Together, these data provide the initial framework of a pathway that can be used to further integrate the molecular events regulating hemangioblast differentiation.

scholarly journals Analysis of maxillopedia Expression Pattern and Larval Cuticular Phenotype in Wild-Type and Mutant Tribolium

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 721-731 ◽  
Author(s):  
Teresa D Shippy ◽  
Jianhua Guo ◽  
Susan J Brown ◽  
Richard W Beeman ◽  
Robin E Denell
Keyword(s):  
Rna Interference ◽  
Expression Pattern ◽  
Tribolium Castaneum ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeotic Gene ◽  
Wild Type ◽  
Double Stranded Rna ◽  
Similar Expression ◽  
Mutant Phenotypes

Abstract The Tribolium castaneum homeotic gene maxillopedia (mxp) is the ortholog of Drosophila proboscipedia (pb). Here we describe and classify available mxp alleles. Larvae lacking all mxp function die soon after hatching, exhibiting strong transformations of maxillary and labial palps to legs. Hypomorphic mxp alleles produce less severe transformations to leg. RNA interference with maxillopedia double-stranded RNA results in phenocopies of mxp mutant phenotypes ranging from partial to complete transformations. A number of gain-of-function (GOF) mxp alleles have been isolated based on transformations of adult antennae and/or legs toward palps. Finally, we have characterized the mxp expression pattern in wild-type and mutant embryos. In normal embryos, mxp is expressed in the maxillary and labial segments, whereas ectopic expression is observed in some GOF variants. Although mxp and Pb display very similar expression patterns, pb null embryos develop normally. The mxp mutant larval phenotype in Tribolium is consistent with the hypothesis that an ancestral pb-like gene had an embryonic function that was lost in the lineage leading to Drosophila.

scholarly journals Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma

2018 ◽  
Vol 25 (2) ◽  
pp. 145-162 ◽  
Author(s):  
Sara Molatore ◽  
Andrea Kügler ◽  
Martin Irmler ◽  
Tobias Wiedemann ◽  
Frauke Neff ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Early Stage ◽  
Pituitary Tumors ◽  
Transcriptome Profiling ◽  
Thyroid Neoplasms ◽  
Recessive Trait ◽  
Wild Type ◽  
Incurable Cancer ◽  
Medullary Thyroid ◽  
Adrenal Pheochromocytoma

Rats affected by the MENX syndrome spontaneously develop multiple neuroendocrine tumors (NETs) including adrenal, pituitary and thyroid gland neoplasms. MENX was initially reported to be inherited as a recessive trait and affected rats were found to be homozygous for the predisposingCdkn1bmutation encoding p27. We here report that heterozygous MENX-mutant rats (p27+/mut) develop the same spectrum of NETs seen in the homozygous (p27mut/mut) animals but with slower progression. Consequently, p27+/mut rats have a significantly shorter lifespan compared with their wild-type (p27+/+) littermates. In the tumors of p27+/mut rats, the wild-typeCdkn1ballele is neither lost nor silenced, implying that p27 is haploinsufficient for tumor suppression in this model. Transcriptome profiling of rat adrenal (pheochromocytoma) and pituitary tumors having different p27 dosages revealed a tissue-specific, dose-dependent effect of p27 on gene expression. In p27+/mut rats, thyroid neoplasms progress to invasive and metastatic medullary thyroid carcinomas (MTCs) accompanied by increased calcitonin levels, as in humans. Comparison of expression signatures of late-stage vs early-stage MTCs from p27+/mut rats identified genes potentially involved in tumor aggressiveness. The expression of a subset of these genes was evaluated in human MTCs and found to be associated with aggressive RET-M918T-positive tumors. Altogether, p27 haploinsufficiency in MENX rats uncovered a novel, representative model of invasive and metastatic MTC exploitable for translational studies of this often aggressive and incurable cancer.

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

scholarly journals Insulin Induces Heterologous Desensitization of G Protein-Coupled Receptor and Insulin-Like Growth Factor I Signaling by Downregulating β-Arrestin-1

2002 ◽  
Vol 22 (17) ◽  
pp. 6272-6285 ◽  
Author(s):  
Stéphane Dalle ◽  
Takeshi Imamura ◽  
David W. Rose ◽  
Dorothy Sears Worrall ◽  
Satoshi Ugi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Insulin Treatment ◽  
Ectopic Expression ◽  
Wild Type ◽  
Factor I ◽  
Igf I ◽  
Heterologous Desensitization ◽  
Kinase Phosphorylation ◽  
G Protein Coupled

ABSTRACT β-Arrestin-1 mediates agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCRs) and is also essential for GPCR mitogenic signaling. In addition, insulin-like growth factor I receptor (IGF-IR) endocytosis is facilitated by β-arrestin-1, and internalization is necessary for IGF-I-stimulated mitogen-activated protein (MAP) kinase activation. Here, we report that treatment of cells for 12 h with insulin (100 ng/ml) induces an ∼50% decrease in cellular β-arrestin-1 content due to ubiquitination of β-arrestin-1 and proteosome-mediated degradation. This insulin-induced decrease in β-arrestin-1 content was blocked by inhibition of phosphatidylinositol-3 kinase (PI-3 kinase) and MEK with wortmannin and PD98059, respectively. We also found a marked decrease in the association of β-arrestin-1 with the IGF-IR and a 55% inhibition of IGF-I-stimulated MAP kinase phosphorylation. In insulin-treated, β-arrestin-1-downregulated cells, there was complete inhibition of lysophosphatidic acid (LPA) or isoproterenol (ISO)-stimulated MAP kinase phosphorylation. This was associated with a decrease in β-arrestin-1 association with the β2-AR as well as a decrease in β-arrestin-1-Src and Src-β2-AR association. Ectopic expression of wild-type β-arrestin-1 in insulin-treated cells in which endogenous β-arrestin-1 had been downregulated rescued IGF-I- and LPA-stimulated MAP kinase phosphorylation. In conclusion, we found the following. (i) Chronic insulin treatment leads to enhanced β-arrestin-1 degradation. (ii) This downregulation of endogenous β-arrestin-1 is associated with decreased IGF-I-, LPA-, and ISO-mediated MAP kinase signaling, which can be rescued by ectopic expression of wild-type β-arrestin-1. (iii) Finally, these results describe a novel mechanism for heterologous desensitization, whereby insulin treatment can impair GPCR signaling, and highlight the importance of β-arrestin-1 as a target molecule for this desensitization mechanism.

scholarly journals Suppressor Mutations Bypass the Requirement of fluG for Asexual Sporulation and Sterigmatocystin Production in Aspergillus nidulans

Genetics ◽  
2003 ◽  
Vol 165 (3) ◽  
pp. 1083-1093
Author(s):  
Jeong-Ah Seo ◽  
Yajun Guan ◽  
Jae-Hyuk Yu
Keyword(s):  
Aspergillus Nidulans ◽  
Molecular Mechanisms ◽  
Dominant Negative ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Mutation ◽  
Asexual Sporulation ◽  
Dominant Negative Mutation ◽  
Suppressor Mutations ◽  
Early Developmental

Abstract Asexual sporulation (conidiation) in the filamentous fungus Aspergillus nidulans requires the early developmental activator fluG. Loss of fluG results in the blockage of both conidiation and production of the mycotoxin sterigmatocystin (ST). To investigate molecular mechanisms of fluG-dependent developmental activation, 40 suppressors of fluG (SFGs) that conidiate without fluG have been isolated and characterized. Genetic analyses showed that an individual suppression is caused by a single second-site mutation, and that all sfg mutations but one are recessive. Pairwise meiotic crosses grouped mutations to four loci, 31 of them to sfgA, 6 of them to sfgB, and 1 each to sfgC and sfgD, respectively. The only dominant mutation, sfgA38, also mapped to the sfgA locus, suggesting a dominant negative mutation. Thirteen sfgA and 1 sfgC mutants elaborated conidiophores in liquid submerged culture, indicating that loss of either of these gene functions not only bypasses fluG function but also results in hyperactive conidiation. While sfg mutants show varying levels of restored conidiation, all recovered the ability to produce ST at near wild-type levels. The fact that at least four loci are defined by recessive sfg mutations indicates that multiple genes negatively regulate conidiation downstream of fluG and that the activity of fluG is required to remove such repressive effects.

pha-4 is Ce-fkh-1, a fork head/HNF-3alpha, beta, gamma homolog that functions in organogenesis of the C. elegans pharynx

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2171-2180 ◽  
Author(s):  
J.M. Kalb ◽  
K.K. Lau ◽  
B. Goszczynski ◽  
T. Fukushige ◽  
D. Moons ◽  
...  
Keyword(s):  
Early Stage ◽  
Sequence Similarity ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Specific Gene ◽  
Gata Factor ◽  
Enhancer Element ◽  
C Elegans ◽  
Fork Head ◽  
Organ Identity

The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3alpha, beta, gamma genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha-4 are the same gene. We show that PHA-4 protein is present in nuclei of essentially all pharyngeal cells, of all five cell types. PHA-4 protein first appears close to the point at which a cell lineage will produce only pharyngeal cells, independently of cell type. We show that PHA-4 binds directly to a ‘pan-pharyngeal enhancer element’ previously identified in the promoter of the pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain protein previously shown to bind a muscle-specific enhancer near the PHA-4 binding site in the myo-2 promoter. We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development. Overall, pha-4 can be described as an ‘organ identity factor’, completely necessary for organ formation, present in all cells of the organ from the earliest stages, capable of integrating upstream developmental pathways (in this case, the two distinct pathways that produce the anterior and posterior pharynx) and participating directly in the transcriptional regulation of organ specific genes. Finally, we note that the distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the distribution of the fork head protein in Drosophila embryos: high levels in the foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut. Overall, our results provide evidence for a highly conserved pathway regulating formation of the digestive tract in all (triploblastic) metazoa.

Isolation and characterization of a downstream target of Pax6 in the mammalian retinal primordium

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3987-3994 ◽  
Author(s):  
Gilbert Bernier ◽  
Wolfgang Vukovich ◽  
Lorenz Neidhardt ◽  
Bernhard G. Herrmann ◽  
Peter Gruss
Keyword(s):  
Transcription Factor ◽  
Expression Pattern ◽  
Large Scale ◽  
Ectopic Expression ◽  
Signal Transduction Pathway ◽  
Homeobox Gene ◽  
Optic Vesicle ◽  
Altered Expression ◽  
Retina Development ◽  
Isolation And Characterization

The transcription factor Pax6 is required for eye morphogenesis in humans, mice and insects, and can induce ectopic eye formation in vertebrate and invertebrate organisms. Although the role of Pax6 has intensively been studied, only a limited number of genes have been identified that depend on Pax6 activity for their expression in the mammalian visual system. Using a large-scale in situ hybridization screen approach, we have identified a novel gene expressed in the mouse optic vesicle. This gene, Necab, encodes a putative cytoplasmic Ca2+-binding protein and coincides with Pax6 expression pattern in the neural ectoderm of the optic vesicle and in the forebrain pretectum. Remarkably, Necab expression is absent in both structures in Pax6 mutant embryos. By contrast, the optic vesicle-expressed homeobox genes Rx, Six3, Otx2 and Lhx2 do not exhibit an altered expression pattern. Using gain-of-function experiments, we show that Pax6 can induce ectopic expression of Necab, suggesting that Necab is a direct or indirect transcriptional target of Pax6. In addition, we have found that Necab misexpression can induce ectopic expression of the homeobox gene Chx10, a transcription factor implicated in retina development. Taken together, our results provide evidence that Necab is genetically downstream of Pax6 and that it is a part of a signal transduction pathway in retina development.

Requirements of Lim1, a Drosophila LIM-homeobox gene, for normal leg and antennal development

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4315-4323 ◽  
Author(s):  
T. Tsuji ◽  
A. Sato ◽  
I. Hiratani ◽  
M. Taira ◽  
K. Saigo ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Border Cells ◽  
Null Mutant ◽  
Tarsal Segment ◽  
Segment Boundary ◽  
Leg Development ◽  
Antagonistic Interactions

During Drosophila leg development, the distal-most compartment (pretarsus) and its immediate neighbour (tarsal segment 5) are specified by a pretarsus-specific homeobox gene, aristaless, and tarsal-segment-specific Bar homeobox genes, respectively; the pretarsus/tarsal-segment boundary is formed by antagonistic interactions between Bar and pretarsus-specific genes that include aristaless (Kojima, T., Sato, M. and Saigo, K. (2000) Development 127, 769–778). Here, we show that Drosophila Lim1, a homologue of vertebrate Lim1 encoding a LIM-homeodomain protein, is involved in pretarsus specification and boundary formation through its activation of aristaless. Ectopic expression of Lim1 caused aristaless misexpression, while aristaless expression was significantly reduced in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by Bar and abolished in leg discs lacking aristaless activity, which was associated with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression occurred upon aristaless misexpression. The concerted function of Lim1 and aristaless was required to maintain Fasciclin 2 expression in border cells and form a smooth pretarsus/tarsal-segment boundary. Lim1 was also required for femur, coxa and antennal development.

scholarly journals Identification of the Telomere elongation mutation in Drosophila

2018 ◽  
Author(s):  
Hemakumar M. Reddy ◽  
Thomas A. Randall ◽  
Radmila Capkova Frydrychova ◽  
James M. Mason
Keyword(s):  
Drosophila Melanogaster ◽  
Next Generation Sequencing ◽  
Ltr Retrotransposons ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Telomere Elongation ◽  
Drosophila Genetic Reference Panel ◽  
Generation Sequencing

Background. Telomeres in Drosophila melanogaster are similar to those of other eukaryotes in terms of their function, although they are formed by non-LTR retrotransposons instead of telomerase-based short repeats. The length of the telomeres in Drosophila depends on the number of copies of these transposable elements. A dominant mutation, Tel1, causes a several-fold elongation of telomeres. Methods. In this study we identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next generation sequencing. Results. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Discussion. The mapped Tel1 mutation (3-bp deletion found in Ino80) did not appear to affect the quantity or length of the Ino80 transcript. Tel1 causes a significant reduction in transcripts of CG18493, a gene nested in an intron 8 of Ino80, which is expressed in ovaries and expected to encode a serine-type peptidase.

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