Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Notch”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed1997

[Magnetic resonance imaging of Kernohan's notch in chronic subdural hematoma].

Compression of the crus cerebri against the free edge of the tentorium contralateral to a supratentorial mass, the so-called Kernohan's notch, can be a cause of false localizing sign. Kernohan's notch has been thoroughly studied clinically and pathologically, but not radiographically. The authors describe a case of left chronic subdural hematoma, which resulted in left hemiparesis caused by Kernohan's notch. Injury to the contralateral cerebral peduncle was clearly shown by magnetic resonance imaging (MRI) performed in the postoperative period. A 43-year-old man was transferred to our hospital in deep coma with dilated pupils, unreactive to light. Computed tomography (CT) scans obtained on admission revealed a left chronic subdural hematoma and a midline shift to the right. After drainage and irrigation of the left chronic subdural hematoma through a single burr hole, his clinical condition improved gradually. But 1 month after the operation, mild left hemiparesis still persisted. MRI T2-weighted images demonstrated an abnormally increased signal area in the right cerebral peduncle. T1-weighted coronal images showed the anatomical relationship between the hypointense lesion in the right cerebral peduncle and tentorial edge. Three-dimensional-MRI (3D-MRI) clearly demonstrated the surface image of Kernohan's notch. We emphasize the utility of 3D-MRI for detecting evidence of brain stem injury, such as Kerno han's notch.

Adult↗
PubMedDate not supplied

[The phenotypic diversity of the disorders of embryogenesis in Notch mutants].

We analyzed embryogenesis of two Notch mutants of Drosophila melanogaster: Notch-84k35 and Notch-88n, and their compounds. Three types of embryonic patterns of the mutants with different doses of gene Notch. Neurogenesis of the head and ventral regions is differentially regulated by gene Notch. Two factors have been identifies that affect the direction of migration of the somatic mesoderm cells. The role of visceral mesoderm in formation of the proventriculus.

Alleles↗
PubMedDate not supplied

[Disordered development of Drosophila melanogaster embryos mosaic for the Notch gene].

Gene Notch codes for a transmembrane protein, which is involved in cell interactions: mutations in Notch locus result in differentiation of all cells of the ventral and anterodorsal ectoderm into neuroblasts. In order to examine interrelations between cells of the normal and mutant phenotype, mosaic embryos were obtained. Procephalic regions of Drosophila trunk were most strongly affected in the experimental, as well as in the control, embryos. In control mosaics, the absence of anterodorsal ectoderm was accompanied by a decrease in the size of epipharyngeal ganglion, whereas Notch mosaics, in contrast, showed the expansion of epipharyngeal ganglion over dorsal ectoderm up to the posterior end of the embryo. Differentiation abnormalities of cells of the ventral ectoderm in Notch mosaics were rarer. Generally, the results of our experiments lead to a hypothesis about the presence of a certain threshold in the proportion between Notch cells and wild-type cells in ventral ectoderm. When this threshold value is exceeded, all cells of ventral ectoderm differentiate into neuroblasts.

Animals↗
PubMed1998

[Notching of the bilateral uterine artery flow velocity wave-forms in the third trimester and perinatal complications].

Pulsatile color duplex Doppler ultrasonography system was used to study blood flow velocity waveforms in the uterine arteries of 492 pregnant women in the third trimester. In 38 (7.7%) patients unilateral and in 42 (8.5%) bilateral postsystolic notches were observed. Those with bilateral early diastolic notches experienced poor perinatal outcome in 40 (95.2%) instances. The same occurred in 16 (42.1%) others with unilateral notches and in 13 (3.2%) without notches but with evidence of increased impedance (pulsatility index > 1.20, resistance index > 0.58 and systolic/diastolic ratio > 2.6). The presence of bilateral postsystolic notches in the uterine artery flow velocity waveforms appears to be a reliable predictor of poor pregnancy outcome.

Adult↗
PubMed1999

Cutting edge: protective effects of notch-1 on TCR-induced apoptosis.

The Notch receptor protein was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions. Members of this family have been isolated from invertebrates as well as vertebrates. We isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77, which is a protein that has been shown previously to be required for apoptosis in T cell lines. The data presented below indicate that Notch-1 expression provides significant protection to T cell lines from TCR-mediated apoptosis. These data demonstrate a new antiapoptotic role for Notch-1, providing evidence that, in addition to regulating cell fate decisions, Notch-1 can play a critical role in controlling levels of cell death in T cells.

Animals↗
PubMed2005

Notch signaling in hematopoiesis and lymphopoiesis: lessons from Drosophila.

The evolutionarily conserved Notch signaling pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal life. It is involved in embryonic organogenesis as well as in the maintenance of homeostasis of self-renewing systems. In this article, we review the role of Notch signaling in the hematopoietic system with particular emphasis on lymphocyte development and highlight the similarities in Notch function between Drosophila and mammalian differentiation processes. Recent studies indicating that aberrant NOTCH signaling is frequently linked to the induction of T leukemia in humans will also be discussed.

Animals↗
PubMed2006

Notch and affinity boundaries in Drosophila.

Cells in multicellular organisms often do not intermingle freely with each other. Differential cell affinities can contribute to organizing cells into different tissues. Drosophila limbs and the vertebrate central nervous system are subdivided into compartments. Cells in adjacent compartments do not mix. Cell interactions mediated by Notch-family receptors have been implicated in the specification of these compartment boundaries. Two recent reports analyze the role of the Notch signaling pathway in the generation of an affinity boundary in the Drosophila wing. The first report analyzes the connection between Notch and the actin cytoskeleton. The second report analyzes the differential requirements of Notch and the transcription factor Suppressor of Hairless in generating the affinity boundary.

Actins↗
PubMed2003

Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells.

The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high-affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro-endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway.

Animals↗
PubMed2006

Nas transgenic mouse line allows visualization of Notch pathway activity in vivo.

The Notch signaling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular, the precise mapping of its sites of activity, remain unclear. To address this issue, we generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jkappa binding sites. Here we show that this transgenic line, which we termed NAS (for Notch Activity Sensor), displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jkappa-deficient background, indicating that it indeed requires Notch/RBP-Jkappa signaling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signaling pathway.

Animals↗
PubMed2004

Inhibition of Notch signaling biases rat thymocyte development towards the NK cell lineage.

Notch receptors are involved in directing the choice between alternative cell fates in developmental scenarios such as thymopoiesis. By pharmacological interference in rat fetal thymus organ culture we show that inhibition of Notch signaling arrests T cell development at an early double-negative stage and is accompanied by a dramatic increase in the number of NK cells. These cells show an activated phenotype, lack recombination of the TCR beta gene locus and express perforin. Similarly, in thymic lobes reconstituted with fetal liver cells, progenitors predominantly develop into NK cells both after pharmacological interference of Notch and after treatment with a recombinant rat Notch1/Fc chimera. Collectively, this identifies the lineage decision of NK/T precursor cells as an important site of Notch action in rat thymocytes.

Amyloid Precursor Protein Secretases↗
PubMed2005

The role of Notch and IL-7 signaling in early thymocyte proliferation and differentiation.

We have analyzed the roles of Notch and IL-7 signaling in the proliferation and differentiation of mouse progenitor thymocyte subpopulations cultured on Notch delta-like-1 ligand-expressing OP9 stromal cells. Using bulk and limiting dilution cultures, we show that DN1 and DN2 cells require both Notch and IL-7 signaling for efficient proliferation and differentiation into cytoplasmic TCRbeta and surface TCRalpha/beta and TCRgamma/delta expressing T cells. Selection for cytoplasmic TCRbeta-positive cells is dependent on preTalpha expression. Both gamma/delta and alpha/beta TCR expressing T cells arising in culture can be efficiently stimulated by anti-CD3 cross-linking, suggesting that they might be functional. The differentiation of adult, but not fetal, DN1 and DN2 thymocytes into CD4 and/or CD8 expressing cells is inhibited by IL-7. Finally, efficient proliferation and differentiation of DN3 cells requires Notch signaling and preTCR expression, but is independent of IL-7.

Cell Differentiation↗
PubMed2004

Notch pathway is dispensable for adipocyte specification.

In the past decade we have witnessed an epidemic of obesity in developed countries. Therefore, understanding the mechanisms involved in regulation of body weight is becoming an increasingly important goal shared by the public and the scientific community. The key to fat deposition is the adipocyte, a specialized cell that plays a critical role in energy balance and appetite regulation. Much of our knowledge of adipogenesis comes from studies using preadipocytic cell lines that have provided important information regarding molecular control of adipocyte differentiation. However, they fall short of revealing how naive cells acquire competence for adipogenesis. Studies in preadipocytes indicate that the Notch pathway plays a role in regulating adipogenesis (Garces et al.: J Biol Chem 272:29729-29734, 1997). Given the known biological functions of Notch in mediating cell fate decisions (Artavanis-Tsakonas et al.: Science 284:770-776, 1999), we wished to test the hypothesis that the Notch pathway is required for this cellular program by examining adipogenesis in several genetic loss-of-function models that encompass the entire pathway. We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors.

Adipocytes↗
PubMed2002

Cortisol regulates the expression of Notch in osteoblasts.

Glucocorticoids have important effects on osteoblastic replication, differentiation, and function, and the Notch family of receptors is considered to play a role in osteoblastic cell differentiation. We postulated that cortisol could regulate Notch and Notch ligand expression in osteoblastic cells, providing an additional mechanism by which glucocorticoids could regulate osteoblastic differentiation. We examined the expression and regulation of Notch1, 2, 3, and 4 and their ligands Jagged 1 and 2 and Delta 1 and 3 by cortisol in cultures of osteoblastic MC3T3-E1 cells. Cortisol caused a time-dependent increase in Notch1 and 2 mRNA levels in MC3T3 cells. Notch3 and 4 were not detected in the presence or absence of cortisol. MC3T3 cells expressed Delta 1 and Jagged 1 but not Jagged 2 or Delta 3 mRNAs, and cortisol did not have a substantial effect on the expression of any of these ligands. Cortisol increased the rate of Notch1 and 2 transcription and, in transcriptionally arrested cells, did not modify the decay of the transcripts, indicating a transcriptional level of control. In conclusion, cortisol stimulates Notch1 and 2 transcription in osteoblasts. Since Notch signaling appears to play a negative role in osteoblastic differentiation, its increased expression could be relevant to the actions of cortisol in bone.

Animals↗
PubMed2004

Taming psoriatic keratinocytes--PTHs' uses go up another notch.

The native parathyroid hormone (PTH) and several of its N-terminal adenylyl cyclase-activating fragments and their analogs have become the star stimulators of bone growth for treating osteoporosis, accelerating fracture healing, and strengthening the anchorage of prosthetic bone implants and one of them (Lilly's Forteo--recombinant hPTH-(1-34) has recently arrived in the clinic. But something entirely different has been lurking in the background-the ability of the adenylyl cyclase stimulating hPTH-(1-34) to calm hyperproliferating keratinocytes and reduce psoriatic lesions. By contrast PTH-(7-34) which cannot stimulate adenylyl cyclase actually stimulates keratinocyte proliferation. Normal keratinocytes make PTHrP after they lift off the basal lamina and have stopped cycling. But they have an unconventional PTH/PTHrP receptor which is not coupled to adenylyl cyclase. Psoriatic keratinocytes do not make PTHrP and have only a broken-down, proliferation-limiting terminal differentiation-driving Notch-Notch ligand mechanism. Putting these and other facts together produces a possible picture of an exogenously applied adenylyl cyclase-activating PTH pinch hitting for the missing PTHrP and restoring normal keratinocyte proliferative activity epidermal structure by stimulating dermal fibroblasts which do have the conventional adenylyl cyclase-linked PTHR1 and in response directly or indirectly restore the overlying basal keratinocytes' Notch-Notch ligand terminal differentiation-driving mechanism and consequently a normal epidermal structure.

Animals↗
PubMed2005

Altered T cell differentiation and Notch signaling induced by the ectopic expression of keratin K10 in the epithelial cells of the thymus.

Transgenic mice expressing hK10 under the keratin K5 promoter display several alterations in the epidermis including decreased cell proliferation, and reduced susceptibility to tumor development. Given that K5 promoter is also active in the epithelial cells of the thymus, we explored the possible alterations of the thymus because of K10 transgene expression. We found severe thymic alterations, which affect not only the thymic epithelial cells (TEC), but also thymocytes. We observed altered architecture and premature thymus involution in the transgenic mice associated with increased apoptosis and reduced proliferation of the thymocytes. Interestingly, prior to the development of this detrimental phenotype, thymocytes of the transgenic mice also displayed altered differentiation, which is aggravated later on. Molecular characterization of this phenotype indicated that Akt activity is reduced in TEC, but not in thymocytes. In addition, we also observed altered expression of Notch family members and some of their ligands both in TEC and T cells. This produces reduced Notch activity in TEC but increased Notch activity in thymocytes, which is detectable prior to the disruption of the thymic architecture. In addition, we also detect altered Notch expression in the epidermis of bK5hK10 transgenic mice. Collectively the present data indicate that keratin K10 may induce severe alterations not only in a cell autonomous manner, but also in neighboring cells by the modulation of signals involved in cell-cell interactions.

Animals↗
PubMed1996

gp300sca is not a high affinity Notch ligand.

The Notch protooncogene encodes a receptor important for determination and differentiation of many cell types, and is conserved between vertebrates and invertebrates. It has been suggested that the secreted protein scabrous (sca) might be a Notch ligand acting in the peripheral nervous system. The sca protein was purified and a cell line expressing 18,000 Notch molecules per cell surface used to test sca binding by coimmunoprecipitation, cell adhesion assays, and binding with labeled sca. No interaction was detected between gp300sca and Notch or the related protein Delta, suggesting that sca acts through a distinct mechanism.

Animals↗
PubMed1999

Mastermind acts downstream of notch to specify neuronal cell fates in the Drosophila central nervous system.

In the Drosophila central nervous system, cellular diversity is generated through the asymmetric partitioning of cell fate determinants at cell division. Neural precursors (or neuroblasts) divide in a stem cell lineage to generate a series of ganglion mother cells, each of which divides once to produce a pair of postmitotic neurons or glial cells. An exception to this rule is the MP2 neuroblast, which divides only once to generate two neurons. We screened for genes expressed in the MP2 neuroblast and its progeny as a means of identifying the factors that specify cell fate in the MP2 lineage. We identified a P-element insertion line that expresses the reporter gene, tau-beta-galactosidase, in the MP2 precursor and its progeny, the vMP2 and dMP2 neurons. The transposon disrupts the neurogenic gene, mastermind, but does not lead to neural hyperplasia. However, the vMP2 neuron is transformed into its sibling cell, dMP2. By contrast, expression of a dominant activated form of the Notch receptor in the MP2 lineage transforms dMP2 to vMP2. Notch signalling requires Mastermind, suggesting that Mastermind acts downstream of Notch to determine the vMP2 cell fate. We show that Mastermind plays a similar role in the neurons derived from ganglion mother cells 1-1a and 4-2a, where it specifies the pCC and RP2sib fates, respectively. This suggests that Notch signalling through Mastermind plays a wider role in specifying neuronal identity in the Drosophila central nervous system.

Animals↗
PubMed2002

Reciprocal regulatory interactions between the Notch and Ras signaling pathways in the Drosophila embryonic mesoderm.

Convergent intercellular signals must be precisely integrated in order to elicit specific biological responses. During specification of muscle and cardiac progenitors from clusters of equivalent cells in the Drosophila embryonic mesoderm, the Ras/MAPK pathway--activated by both epidermal and fibroblast growth factor receptors--functions as an inductive cellular determination signal, while lateral inhibition mediated by Notch antagonizes this activity. A critical balance between these signals must be achieved to enable one cell of an equivalence group to segregate as a progenitor while its neighbors assume a nonprogenitor identity. We have investigated whether these opposing signals directly interact with each other, and we have examined how they are integrated by the responding cells to specify their unique fates. Our findings reveal that Ras and Notch do not function independently; rather, we have uncovered several modes of cross-talk between these pathways. Ras induces Notch, its ligand Delta, and the epidermal growth factor receptor antagonist, Argos. We show that Delta and Argos then synergize to nonautonomously block a positive autoregulatory feedback loop that amplifies a fate-inducing Ras signal. This feedback loop is characterized by Ras-mediated upregulation of proximal components of both the epidermal and fibroblast growth factor receptor pathways. In turn, Notch activation in nonprogenitors induces its own expression and simultaneously suppresses both Delta and Argos levels, thereby reinforcing a unidirectional inhibitory response. These reciprocal interactions combine to generate the signal thresholds that are essential for proper specification of progenitors and nonprogenitors from groups of initially equivalent cells.

Animals↗