Sloppy paired acts as the downstream target of wingless in the Drosophila CNS and interaction between sloppy paired and gooseberry inhibits sloppy paired during neurogenesis

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 655-665 ◽  
Author(s):  
K.M. Bhat ◽  
E.H. van Beers ◽  
P. Bhat
Keyword(s):  
Target Gene ◽  
Ectopic Expression ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Heterologous Promoter ◽  
Neuronal Precursor ◽  
Downstream Target ◽  
Wnt Proteins ◽  
Neuronal Lineage ◽  
Neuronal Precursor Cell

Wingless (Wg) and other Wnt proteins play a crucial role in a number of developmental decisions in a variety of organisms. In the ventral nerve cord of the Drosophila embryo, Wg is non-autonomously required for the formation and specification of a neuronal precursor cell, NB4-2. NB4-2 gives rise to a well-studied neuronal lineage, the RP2/sib lineage. While the various components of the Wg-signaling pathway are also required for generating NB4-2, the target gene(s) of this pathway in the signal-receiving cell is not known. In this paper, we show that sloppy paired 1 and sloppy paired 2 function as the downstream targets of the Wg signaling to generate the NB4-2 cell. Thus, while the loss-of-function mutations in wg and slp have the same NB4-2 formation and specification defects, these defects in wg mutants can be rescued by expressing slp genes from a heterologous promoter. That slp genes function downstream of the Wg signaling is also indicated by the result that expression of slp genes is lost from the neuroectoderm in wg mutants and that ectopic expression of wg induces ectopic expression of slp. Finally, previous results show that Gooseberry (Gsb) prevents Wg from specifying NB4-2 identity to the wg-expressing NB5-3. In this paper, we also show that gsb interacts with slp and prevents Slp from specifying NB4-2 identity. Overexpression of slp overcomes this antagonistic interaction and respecifies NB5-3 as NB4-2. This respecification, however, can be suppressed by a simultaneous overexpression of gsb at high levels. This mechanism appears to be responsible for specifying NB5-3 identity to a row 5 neuroblast and preventing Wg from specifying NB4-2 identity to that cell.

Regulation of a dpp target gene in the Drosophila embryo

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 303-311 ◽  
Author(s):  
J. Rusch ◽  
M. Levine
Keyword(s):  
Target Gene ◽  
Fusion Gene ◽  
Drosophila Embryo ◽  
Specific Expression ◽  
Downstream Target ◽  
Embryonic Tissues ◽  
Posterior Midgut ◽  
Downstream Target Gene ◽  
Genetic Epistasis ◽  
Vp16 Fusion

In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknullt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa.

The role of the NK-homeobox gene slouch (S59) in somatic muscle patterning

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4525-4535 ◽  
Author(s):  
S. Knirr ◽  
N. Azpiazu ◽  
M. Frasch
Keyword(s):  
Muscle Development ◽  
Ectopic Expression ◽  
Homeobox Gene ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Cell Fates ◽  
Somatic Muscle ◽  
Gene Encoding ◽  
Body Wall Muscles ◽  
Founder Cells

In the Drosophila embryo, a distinct class of myoblasts, designated as muscle founders, prefigures the mature pattern of somatic body wall muscles. Each founder cell appears to be instrumental in generating a single larval muscle with a defined identity. The NK homeobox gene S59 was the first of a growing number of proposed ‘identity genes’ that have been found to be expressed in stereotyped patterns in specific subsets of muscle founders and their progenitor cells and are thought to control their developmental fates. In the present study, we describe the effects of gain- and loss-of-function experiments with S59. We find that a null mutation in the gene encoding S59, which we have named slouch (slou), disrupts the development of all muscles that are derived from S59-expressing founder cells. The observed phenotypes upon mutation and ectopic expression of slouch include transformations of founder cell fates, thus confirming that slouch (S59) functions as an identity gene in muscle development. These fate transformations occur between sibling founder cells as well as between neighboring founders that are not lineage-related. In the latter case, we show that slouch (S59) activity is required cell-autonomously to repress the expression of ladybird (lb) homeobox genes, thereby preventing specification along the lb pathway. Together, these findings provide new insights into the regulatory interactions that establish the somatic muscle pattern.

scholarly journals Hairless is a cofactor for Runt-dependent transcriptional regulation

2011 ◽  
Vol 22 (8) ◽  
pp. 1364-1374 ◽  
Author(s):  
Pegine B. Walrad ◽  
Saiyu Hang ◽  
J. Peter Gergen
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Interactions ◽  
Target Gene ◽  
Transcriptional Regulator ◽  
Drosophila Embryo ◽  
Functional Requirements ◽  
Developmental Pathway ◽  
Downstream Target ◽  
Early Drosophila Embryo ◽  
Cellular Context

Runt is a vital transcriptional regulator in the developmental pathway responsible for segmentation in the Drosophila embryo. Runt activates or represses transcription in a manner that is dependent on both cellular context and the specific downstream target. Here we identify Hairless (H) as a Runt-interacting molecule that functions during segmentation. We find that H is important for maintenance of engrailed (en) repression as was previously demonstrated for Groucho (Gro), Rpd3, and CtBP. H also contributes to the Runt-dependent repression of sloppy-paired-1 (slp1), a role that is not shared with these other corepressors. We further find distinct roles for these different corepressors in the regulation of other Runt targets in the early Drosophila embryo. These findings, coupled with observations on the distinct functional requirements for Runt in regulating these several different targets, indicate that Runt-dependent regulation in the Drosophila blastoderm embryo relies on unique, target-gene-specific molecular interactions.

scholarly journals Undulated short-tail Deletion Mutation in the Mouse Ablates Pax1 and Leads to Ectopic Activation of Neighboring Nkx2-2 in Domains That Normally Express Pax1

Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 299-307
Author(s):  
Chikara Kokubu ◽  
Bettina Wilm ◽  
Tomoko Kokubu ◽  
Matthias Wahl ◽  
Isabel Rodrigo ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Ectopic Expression ◽  
Deletion Mutation ◽  
Loss Of Function ◽  
Downstream Target ◽  
Short Tail ◽  
Ectopic Activation ◽  
Or Genes ◽  
Null Mutants ◽  
Antisense Genes

Abstract Previous studies have indicated that the Undulated short-tail deletion mutation in mouse Pax1 (Pax1Un-s) not only ablates Pax1, but also disturbs a gene or genes nearby Pax1. However, which gene(s) is involved and how the Pax1Un-s phenotype is confined to the Pax1-positive tissues remain unknown. In the present study, we determined the Pax1Un-s deletion interval to be 125 kb and characterized genes around Pax1. We show that the Pax1Un-s mutation affects four physically linked genes within or near the deletion, including Pax1, Nkx2-2, and their potential antisense genes. Remarkably, Nkx2-2 is ectopically activated in the sclerotome and limb buds of Pax1Un-s embryos, both of which normally express Pax1. This result suggests that the Pax1Un-s deletion leads to an illegitimate interaction between remotely located Pax1 enhancers and the Nkx2-2 promoter by disrupting an insulation mechanism between Pax1 and Nkx2-2. Furthermore, we show that expression of Bapx1, a downstream target of Pax1, is more strongly affected in Pax1Un-s mutants than in Pax1-null mutants, suggesting that the ectopic expression of Nkx2-2 interferes with the Pax1-Bapx1 pathway. Taken together, we propose that a combination of a loss-of-function mutation of Pax1 and a gain-of-function mutation of Nkx2-2 is the molecular basis of the Pax1Un-s mutation.

Exosomal hsa_circ_0007047 Attenuates Pos-myocardial Infarction Remodeling by Promoting Angiogenesis via miR-1178-3p/PDPK1 Axis

2021 ◽  
Author(s):  
Shuai MAO ◽  
Yubin Liang ◽  
Ling Yu ◽  
Minzhou Zhang ◽  
Phillip C. Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Target Gene ◽  
Normal Subjects ◽  
Left Ventricular ◽  
Border Zone ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Downstream Target

Abstract Emerging studies indicate that exosomes and their inner noncoding RNAs, especially circular RNAs (circRNAs), play key roles in gene regulatory network and cardiovascular repair. However, our understanding of exosomal circRNAs on cardiac remodeling after myocardial infarction (MI) remains limited. In the present study, exosomes were harvested from the serum of patients with and without postinfarction cardiac remodeling. The results showed that the level of hsa_circ_0007047 was significantly downregulated in serum exosome of patients with the adverse cardiac remodeling when compared with those without post-MI remodeling or normal subjects. Loss-of-function approaches in vitro established that exosomal hsa_circ_0007047 robustly promoted angiogenesis and stimulated of cultured human vascular smooth muscle cells proliferation and migration. Accordingly, overexpression of exosomal hsa_circ_0007047 in mice significantly attenuated MI-induced myocardial fibrosis and left ventricular dysfunction, accompanied by a larger functional capillary network at the border zone. Further exploration of the downstream target gene indicated that hsa_circ_0007047 acts as a competing endogenous RNA by directly binding to miR-1178-3p and thereby inducing transcription of its target gene phosphoinositide-dependent kinase-1 (PDPK1), a critical positive regulatory factor of angiogenesis. Together, our results revealed that exosomal hsa_circ_0007047 attenuated detrimental post-MI remodeling via miR-1178-3p/PDPK1 axis, which facilitated revascularization, ultimately improved the cardiac function.

The Regulation of Downstream Target Gene AP-2γ by Transcription Factor OCT-4

2013 ◽  
Vol 40 (1) ◽  
pp. 43
Author(s):  
Xiao-Meng ZHAO ◽  
Cheng WANG ◽  
Xiao-Feng LI ◽  
Xiao-Ting ZHANG ◽  
Xi-Zhi LIU ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Gene ◽  
Downstream Target ◽  
Downstream Target Gene

Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis

2019 ◽  
Vol 20 (6) ◽  
pp. 625-634 ◽  
Author(s):  
Xun Che ◽  
Wei Dai
Keyword(s):  
Target Gene ◽  
Tumor Development ◽  
Environmental Response ◽  
Carcinogenic Effect ◽  
Post Translational Modifications ◽  
Downstream Target ◽  
Aryl Hydrocarbon ◽  
Downstream Target Gene ◽  
Major Mediator

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

scholarly journals Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luyao Wu ◽  
Yu Ding ◽  
Houchao Tong ◽  
Xi Zhuang ◽  
Jingsheng Cai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Noncoding Rna ◽  
Animal Experiments ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Loss Of Function ◽  
Functional Roles

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. Methods The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). Results Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. Conclusions This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

scholarly journals Partitioning of N-Ethylmaleimide-Sensitive Fusion (NSF) Protein Function in Drosophila melanogaster: dNSF1 Is Required in the Nervous System, and dNSF2 Is Required in Mesoderm

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 265-278
Author(s):  
Jessica A Golby ◽  
Leigh Anna Tolar ◽  
Leo Pallanck
Keyword(s):  
Nervous System ◽  
Protein Function ◽  
Ectopic Expression ◽  
Drosophila Genome ◽  
Loss Of Function ◽  
Stage Of Development ◽  
Expression Studies ◽  
Larval Nervous System ◽  
Constitutive Secretion ◽  
Temporal And Spatial

Abstract The N-ethylmaleimide-sensitive fusion protein (NSF) promotes the fusion of secretory vesicles with target membranes in both regulated and constitutive secretion. While it is thought that a single NSF may perform this function in many eukaryotes, previous work has shown that the Drosophila genome contains two distinct NSF genes, dNSF1 and dNSF2, raising the possibility that each plays a specific secretory role. To explore this possibility, we generated mutations in the dNSF2 gene and used these and novel dNSF1 loss-of-function mutations to analyze the temporal and spatial requirements and the degree of functional redundancy between dNSF1 and dNSF2. Results of this analysis indicate that dNSF1 function is required in the nervous system beginning at the adult stage of development and that dNSF2 function is required in mesoderm beginning at the first instar larval stage of development. Additional evidence suggests that dNSF1 and dNSF2 may play redundant roles during embryonic development and in the larval nervous system. Ectopic expression studies demonstrate that the dNSF1 and dNSF2 gene products can functionally substitute for one another. These results indicate that the Drosophila NSF proteins exhibit similar functional properties, but have evolved distinct tissue-specific roles.

scholarly journals Identification of Autosomal Regions Involved in Drosophila Raf Function

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 763-774 ◽  
Author(s):  
Willis Li ◽  
Elizabeth Noll ◽  
Norbert Perrimon
Keyword(s):  
Limb Development ◽  
Target Gene ◽  
Biological Function ◽  
Genetic Interaction ◽  
Ectopic Expression ◽  
Tor Signaling ◽  
Downstream Effector ◽  
Early Embryos ◽  
Genomic Regions

Abstract Raf is an essential downstream effector of activated p21Ras (Ras) in transducing proliferation or differentiation signals. Following binding to Ras, Raf is translocated to the plasma membrane, where it is activated by a yet unidentified “Raf activator.” In an attempt to identify the Raf activator or additional molecules involved in the Raf signaling pathway, we conducted a genetic screen to identify genomic regions that are required for the biological function of Drosophila Raf (Draf). We tested a collection of chromosomal deficiencies representing ∼70% of the autosomal euchromatic genomic regions for their abilities to enhance the lethality associated with a hypomorphic viable allele of Draf, DrafSu2. Of the 148 autosomal deficiencies tested, 23 behaved as dominant enhancers of Draf  Su2, causing lethality in Draf  Su2 hemizygous males. Four of these deficiencies identified genes known to be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl, encoding a MAPK), 14-3-3ϵ, and bowel (bowl). Two additional deficiencies removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate that Src64B interacts genetically with Draf and that an activated form of Src64B, when overexpressed in early embryos, causes ectopic expression of the Torso (Tor) receptor tyrosine kinase-target gene tailless. In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These results suggest that Tec29A and Src64B are involved in Tor signaling, raising the possibility that they function to activate Draf. Finally, we discovered a genetic interaction between Draf  Su2 and Df(3L)vin5 that revealed a novel role of Draf in limb development. We find that loss of Draf activity causes limb defects, including pattern duplications, consistent with a role for Draf in regulation of engrailed (en) expression in imaginal discs.

Sign in / Sign up

Export Citation Format

Share Document