Disease relevance of notch1-a

• In addition, elevated Notch signaling in the pronephric anlage both perturbed the characteristic pattern of the differentiated tubule network and increased the expression of early markers of pronephric precursor cells, Pax-2 and Wilms' tumor suppressor gene (Wt-1) [1].

Psychiatry related information on notch1-a

• The data presented here suggest that Notch control of differentiation may involve activation of transcription of Id, a negative regulator of bHLH transcription factors [2].

High impact information on notch1-a

• Expression of this gene is positively regulated by the bHLH protein X-NGNR-1 and negatively regulated by the Notch/Delta signal transduction pathway [3].
• One of these genes, the Notch gene from Drosophila, is involved with cell fate choices in the neurogenic region of the blastoderm, in the developing nervous system, and in the eye-antennal imaginal disc [4].
• Nrarp is a member of the Delta-Notch synexpression group and encodes a small protein containing two ankyrin repeats [5].
• During the development of the vertebrate embryo, genes encoding components of the Notch signaling pathway are required for subdividing the paraxial mesoderm into repeating segmental structures, called somites [6].
• These results indicate that a hallmark of neural cell fate determination, i.e. the feedback loop between differentiation promoting basic helix-loop-helix proteins and the Notch regulatory circuitry, is conserved in myogenesis, supporting a direct involvement of Notch in muscle determination [7].

Biological context of notch1-a

• To better understand this effect and the mechanism of LMC itself, we investigated at which step of activin signal transduction pathway the Notch signaling act to affect the timing of the LMC [8].
• Here, we address this issue by identifying enhancers driving Notch-dependent gene expression of two Hes5-like genes expressed in Xenopus called Esr1 and Esr10 [9].
• Here, we show that the Xenopus Hairy-related transcription factor (HRT) gene XHRT1, and the Hairy/Enhancer of split (HES) genes Xhairy1, Xhairy2b, esr9 and esr10, have distinct restricted dynamic expression patterns during pronephros development, and that their expression is regulated by Notch [10].
• We found that Notch activation in this system caused cells to exit the cell cycle prematurely, and when it is misexpressed with Xath5, it also potentiates the induction of RGCs [11].
• Using deletion and mutation analysis, we define motifs required for enhancer activity of both genes, namely Notch-responsive elements and, in the case of Esr10, E-box motifs [9].

Anatomical context of notch1-a

• Here we show that the muscle-determining factor MyoD is a direct, positive regulator of the Notch ligand Delta-1 in prospective myoblasts of the pre-involuted mesoderm in Xenopus gastrulae [7].
• We propose that within a population of the early organiser with equivalent potential to develop either as notochord or floor plate, Notch activation favours floor plate development at the expense of the notochord, preferentially before mid gastrula [12].
• This pattern arises during early development when cells within the inner layer of ectoderm are selected out by Notch to form ciliated cell precursors (CCPs) that then radially intercalate into the outer epithelial cell layer to form ciliated cells [13].
• Activation of the Notch pathway, specifically in gastrula stage embryos, results in a dramatic decrease in the expression of genes necessary to create many different types of mesodermal tissues while causing a dramatic expansion of endodermal tissue markers [14].
• Our findings demonstrate a much broader role for Notch signaling during germ layer determination than previously reported in a vertebrate organism [14].

Associations of notch1-a with chemical compounds

• Altering segmental identity in embryos by perturbing the activity of Thylacine 1 and the Notch pathway, or by treatment with a protein synthesis inhibitor, cycloheximide, leads to the predicted changes in the segmental expression of PAPC [15].
• In the Xenopus pronephros, Evi1 expression is upregulated by retinoid signaling and repressed by overexpression of xWT1 and by Notch signaling [16].
• Bisphenol A Causes Malformation of the Head Region in Embryos of Xenopus laevis and Decreases the Expression of the ESR-1 Gene Mediated by Notch Signaling [17].
• This sequential process is governed by the activation and regulation of Notch-related molecular oscillators by fibroblast growth factor and retinoic acid (RA) signaling [18].

Regulatory relationships of notch1-a

• Combined expression of Xwnt3a and active Notch in animal cap explants is sufficient to induce Xhox3, provoke elongation and form neural tubes [19].
• The ectopic expression of nrp-1 was not inhibited by co-injection of XMam1 with a molecule known to inhibit Notch signaling [20].

Other interactions of notch1-a

• Moreover, we propose a bi-directional signaling pathway mediated by X-Serrate-1 in Notch signaling [21].
• XMam1, Xenopus Mastermind1, induces neural gene expression in a Notch-independent manner [20].
• To assess the effect of Xenopus Dishevelled (Xdsh), a proposed component of the Wnt, Notch and Frizzled signal transduction pathways, on AP axis determination, it was supplied in varying doses to presumptive ectodermal cells [22].
• This choice is under the control of lateral inhibition mediated by a Suppressor of Hairless-dependent Notch signaling pathway, in which X-Delta-1 is the putative ligand driving the selection process, and a new Enhancer-of-Split-related gene is an epidermal target of Notch signaling [23].
• We show that Thylacine 1 and the Notch pathway establish segment identity one segment prior to the segmental expression of PAPC [15].

References