The patched signaling pathway mediates repression of gooseberry allowing neuroblast specification by wingless during Drosophila neurogenesis

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2921-2932 ◽  
Author(s):  
K.M. Bhat
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Transmembrane Protein ◽  
Ectopic Expression ◽  
Negative Regulation ◽  
Dependent Manner ◽  
Neuronal Precursor ◽  
System A ◽  
Developing Nervous System

The Drosophila signaling molecule Wingless (Wg) plays crucial roles in cell-cell communications during development. In the developing nervous system, a previous study has shown that Wg acts non-autonomously to specify the fate of a specific neuronal precursor, NB4-2 (Q. Chu-LaGraff and C. Q. Doe (1993) Science 261, 1594–1597). The lack of autocrine specification of NB4-2 in Wg-expressing cells suggests that the response to Wg is spatially restricted, presumably through the activity of the Wg-receptor. I show that two other proteins, a transcription factor Gooseberry (Gsb) and a transmembrane protein Patched (Ptc), participate in the Wg-mediated specification of NB4-2 by controlling the response to the Wg signal. In gsb mutants, Wg-positive NB5-3 is transformed to NB4-2 in a Wg-dependent manner, suggesting that Gsb normally represses the capacity to respond to the Wg signal. In ptc mutants, Gsb is ectopically expressed in normally Wg-responsive cells, thus preventing the Wg response and consequently the correct specification of NB4-2 does not take place. This conclusion is supported by the observation that NB4-2 can be specified in gsb;ptc double mutants in a Wg-dependent manner. Moreover, ectopic expression of Gsb from the hsp7O-gsb transgene also blocks the response to the Wg signal. I propose that the responsiveness to the Wg signal is controlled by sequential negative regulation, ptc-->gsb-->Wg receptor. The timing of the response to Gsb suggests that the specification of neuroblast identities takes place within the neuroectoderm, prior to neuroblast delamination.

NeuroM, a neural helix-loop-helix transcription factor, defines a new transition stage in neurogenesis

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3263-3272 ◽  
Author(s):  
T. Roztocil ◽  
L. Matter-Sadzinski ◽  
C. Alliod ◽  
M. Ballivet ◽  
J.M. Matter
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Mitotic Cycle ◽  
Ventricular Zone ◽  
Helix Loop Helix ◽  
E Box ◽  
Genes Encoding ◽  
Developing Nervous System

Genes encoding transcription factors of the helix-loop-helix family are essential for the development of the nervous system in Drosophila and vertebrates. Screens of an embryonic chick neural cDNA library have yielded NeuroM, a novel neural-specific helix-loop-helix transcription factor related to the Drosophila proneural gene atonal. The NeuroM protein most closely resembles the vertebrate NeuroD and Nex1/MATH2 factors, and is capable of transactivating an E-box promoter in vivo. In situ hybridization studies have been conducted, in conjunction with pulse-labeling of S-phase nuclei, to compare NeuroM to NeuroD expression in the developing nervous system. In spinal cord and optic tectum, NeuroM expression precedes that of NeuroD. It is transient and restricted to cells lining the ventricular zone that have ceased proliferating but have not yet begun to migrate into the outer layers. In retina, NeuroM is also transiently expressed in cells as they withdraw from the mitotic cycle, but persists in horizontal and bipolar neurons until full differentiation, assuming an expression pattern exactly complementary to NeuroD. In the peripheral nervous system, NeuroM expression closely follows cell proliferation, suggesting that it intervenes at a similar developmental juncture in all parts of the nervous system. We propose that availability of the NeuroM helix-loop-helix factor defines a new stage in neurogenesis, at the transition between undifferentiated, premigratory and differentiating, migratory neural precursors.

scholarly journals Evidence for the critical role of the PI3K signaling pathway in particulate matter-induced dysregulation of the inflammatory mediators COX-2/PGE2 and the associated epithelial barrier protein Filaggrin in the bronchial epithelium

2019 ◽  
Vol 36 (4) ◽  
pp. 301-313
Author(s):  
Chenjian Song ◽  
Lingjing Liu ◽  
Junjie Chen ◽  
Yiran Hu ◽  
Jingli Li ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Airway Inflammation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Pi3k Signaling ◽  
Dependent Manner ◽  
Pi3k Signaling Pathway ◽  
Cox 2

AbstractParticulate matter (PM) is an environmental pollutant closely associated with human airway inflammation. However, the molecular mechanisms of PM-related airway inflammation remains to be fully elucidated. It is known that COX-2/PGE2 play key roles in the pathogenesis of airway inflammation. Filaggrin is a transmembrane protein contributing to tight junction barrier function. As such, Filaggrin prevents leakage of transported solutes and is therefore necessary for the maintenance of epithelial integrity. The objective of the present study was to investigate the regulatory mechanisms of COX-2/PGE2 and Filaggrin upon PM exposure both in vivo and in vitro. C57BL/6 mice received intratracheal instillation of PM for two consecutive days. In parallel, human bronchial epithelial cells (HBECs) were exposed to PM for 24 h. PM exposure resulted in airway inflammation together with upregulation of COX-2/PGE2 and downregulation of Filaggrin in mouse lungs. Corresponding dysregulation of COX-2/PGE2 and Filaggrin was also observed in HBECs subjected to PM. PM exposure led to the phosphorylation of ERK, JNK, and PI3K signaling pathways in a time-dependent manner, while blockade of PI3K with the specific molecular inhibitor LY294002 partially reversed the dysregulation of COX-2/PGE2 and Filaggrin. Moreover, pretreatment of HBECs with NS398, a specific molecular inhibitor of COX-2, and AH6809, a downstream PGE2 receptor inhibitor, reversed the downregulation of Filaggrin upon PM exposure. Taken together, these data demonstrated that the PI3K signaling pathway upregulated COX-2 as well as PGE2 and acted as a pivotal mediator in the downregulation of Filaggrin.

Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner

2020 ◽  
Vol 29 (4) ◽  
pp. 521-529
Author(s):  
Yong Yin ◽  
Keke Yang ◽  
Juanjuan Li ◽  
Peng Da ◽  
Zhenxin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Transmembrane Protein ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Normal Tissues

OBJECTIVE: To assess the expression levels of IFITM1 in human tissue samples and laryngeal squamous cell carcinoma (LSCC) cells, and to explore the potential mechanisms of IFITM1 in LSCC progression. METHODS: Quantitative PCR and immunohistochemical (IHC) assays were performed to detect IFITM1 expression in 62 LSCC tissues and corresponding normal tissues. We further detected the effects of IFITM1 on the proliferation, migration and invasion of LSCC cells and NF-κB signaling pathway through colony formation assay, wound healing assay and transwell assay, respectively. RESULTS: We demonstrated the possible involvement of IFITM1 in the progression of LSCC. We found the upregulated expression of IFITM1 in human LSCC tissues and cells, and analyzed the correlations between IFITM1 expression and osteopontin. Our data further confirmed that IFITM1 affected cell proliferation, migration, and invasion of LSCC cells via the regulation of NF-κB signaling pathway. CONCLUSIONS: We investigated the potential involvement of IFITM1 in the progression of LSCC, and therefore confirmed that IFITM1 was a potential therapeutic target for LSCC.

scholarly journals Drosophila Zic family member odd-paired is needed for adult post-ecdysis maturation

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190245
Author(s):  
Eléanor Simon ◽  
Sergio Fernández de la Puebla ◽  
Isabel Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Family Member ◽  
Ectopic Expression ◽  
Functional Conservation ◽  
The Central Nervous System ◽  
Behavioural Sequence

Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster , the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologue Zic2 , in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.

scholarly journals Forkhead Transcription Factor FKHR-L1 Modulates Cytokine-Dependent Transcriptional Regulation of p27KIP1

2000 ◽  
Vol 20 (24) ◽  
pp. 9138-9148 ◽  
Author(s):  
Pascale F. Dijkers ◽  
Rene H. Medema ◽  
Cornelieke Pals ◽  
Lolita Banerji ◽  
N. Shaun B. Thomas ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Cell Survival ◽  
Kinase Inhibitor ◽  
Ectopic Expression ◽  
Dependent Manner ◽  
Forkhead Transcription Factor ◽  
Protein Levels ◽  
Macrophage Colony ◽  
Null Mutant Mice

ABSTRACT Interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor regulate the survival, proliferation, and differentiation of hematopoietic lineages. Phosphatidylinositol 3-kinase (PI3K) has been implicated in the regulation of these processes. Here we investigate the molecular mechanism by which PI3K regulates cytokine-mediated proliferation and survival in the murine pre-B-cell line Ba/F3. IL-3 was found to repress the expression of the cyclin-dependent kinase inhibitor p27KIP1 through activation of PI3K, and this occurs at the level of transcription. This transcriptional regulation occurs through modulation of the forkhead transcription factor FKHR-L1, and IL-3 inhibited FKHR-L1 activity in a PI3K-dependent manner. We have generated Ba/F3 cell lines expressing a tamoxifen-inducible active FKHR-L1 mutant [FKHR-L1(A3):ER*]. Tamoxifen-mediated activation of FKHR-L1(A3):ER* resulted in a striking increase in p27KIP1 promoter activity and mRNA and protein levels as well as induction of the apoptotic program. The level of p27KIP1 appears to be critical in the regulation of cell survival since mere ectopic expression of p27KIP1 was sufficient to induce Ba/F3 apoptosis. Moreover, cell survival was increased in cytokine-starved bone marrow-derived stem cells from p27KIP1 null-mutant mice compared to that in cells from wild-type mice. Taken together, these observations indicate that inhibition of p27KIP1transcription through PI3K-induced FKHR-L1 phosphorylation provides a novel mechanism of regulating cytokine-mediated survival and proliferation.

A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3221-3232 ◽  
Author(s):  
J.R. McWhirter ◽  
M. Goulding ◽  
J.A. Weiner ◽  
J. Chun ◽  
C. Murre
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Target Genes ◽  
Representational Difference Analysis ◽  
Bhlh Transcription Factor ◽  
Fibroblast Growth ◽  
Downstream Target ◽  
Developing Nervous System

Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome translocation, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs.

scholarly journals The Developing Nervous System: A Series of Review Articles: Neurobiology of Hypoxic-Ischemic Injury in the Developing Brain

2001 ◽  
Vol 49 (6) ◽  
pp. 735-741 ◽  
Author(s):  
Michael V Johnston ◽  
William H Trescher ◽  
Akira Ishida ◽  
Wako Nakajima ◽  
Alvin Zipursky
Keyword(s):  
Nervous System ◽  
Ischemic Injury ◽  
Developing Brain ◽  
System A ◽  
Review Articles ◽  
Developing Nervous System ◽  
Hypoxic Ischemic Injury
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