Non-canonical activation of Notch signaling/target genes in vertebrates

Sanalkumar, Rajendran; Dhanesh, Sivadasan Bindu; James, Jackson

doi:10.1007/s00018-010-0391-x

Cited by 78 publications

(52 citation statements)

References 105 publications

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“…Besides binding to RBPJκ, N1ICD interacts with a range of different transcription factors (65), of which HIF1α, NFκB, GABPA, and ZNF143 are also detected in our previously published microarray data (66) of EGFR + CTBs (accessible at Gene Expression Omnibus, GDS3523). Moreover, RBPJκ has Notch-independent roles in different cell types, mostly as suppressor of gene transcription (67).…”

Section: Discussionmentioning

confidence: 99%

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Haider

Meinhardt

Saleh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

124

144

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Development of the human placenta and its different epithelial trophoblasts is crucial for a successful pregnancy. Besides fusing into a multinuclear syncytium, the exchange surface between mother and fetus, progenitors develop into extravillous trophoblasts invading the maternal uterus and its spiral arteries. Migration into these vessels promotes remodelling and, as a consequence, adaption of blood flow to the fetal–placental unit. Defects in remodelling and trophoblast differentiation are associated with severe gestational diseases, such as preeclampsia. However, mechanisms controlling human trophoblast development are largely unknown. Herein, we show that Notch1 is one such critical regulator, programming primary trophoblasts into progenitors of the invasive differentiation pathway. At the 12th wk of gestation, Notch1 is exclusively detected in precursors of the extravillous trophoblast lineage, forming cell columns anchored to the uterine stroma. At the 6th wk, Notch1 is additionally expressed in clusters of villous trophoblasts underlying the syncytium, suggesting that the receptor initiates the invasive differentiation program in distal regions of the developing placental epithelium. Manipulation of Notch1 in primary trophoblast models demonstrated that the receptor promotes proliferation and survival of extravillous trophoblast progenitors. Notch1 intracellular domain induced genes associated with stemness of cell columns, myc and VE-cadherin, in Notch1−fusogenic precursors, and bound to themycpromoter and enhancer region at RBPJκ cognate sequences. In contrast, Notch1 repressed syncytialization and expression of TEAD4 and p63, two regulators controlling self-renewal of villous cytotrophoblasts. Our results revealed Notch1 as a key factor promoting development of progenitors of the extravillous trophoblast lineage in the human placenta.

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Section: Discussionmentioning

confidence: 99%

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Haider

Meinhardt

Saleh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

124

144

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“…NICD activation could activate RBP-Jk to directly activate the p63 promoter, which contains putative RBP-Jk binding sites (data not shown). Alternatively, non-canonical Notch signaling may be involved by interacting with alternative signaling pathways such as FGF, Shh and Wnt signaling (Sanalkumar et al, 2010). Noncanonical Notch signaling in the skin occurs given the different phenotypes of conditional genetic mouse models lacking a functional γ-secretase complex (presenelin 1/2; PS1/PS2), the Notch receptors (Notch1/2; N1/N2) or the RBP-Jk transcriptional repressor (Demehri and Kopan, 2009).…”

Section: Research Articlementioning

confidence: 99%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

Horsley

2013

Development

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MiceK14-H2BGFP transgenic mice (Tumbar et al., 2004) SUMMARYThe development of the mature epidermis requires a coordinated sequence of signaling events and transcriptional changes to specify surface ectodermal progenitor cells to the keratinocyte lineage. The initial events that specify epidermal keratinocytes from ectodermal progenitor cells are not well understood. Here, we use both developing mouse embryos and human embryonic stem cells (hESCs) to explore the mechanisms that direct keratinocyte fate from ectodermal progenitor cells. We show that both hESCs and murine embryos express p63 before keratin 14. Furthermore, we find that Notch signaling is activated before p63 expression in ectodermal progenitor cells. Inhibition of Notch signaling pharmacologically or genetically reveals a negative regulatory role for Notch signaling in p63 expression during ectodermal specification in hESCs or mouse embryos, respectively. Taken together, these data reveal a role for Notch signaling in the molecular control of ectodermal progenitor cell specification to the epidermal keratinocyte lineage.

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“…These results might thus be consistent with the notion that MamL1 and MamL3 function in the same pathway as RBP-J and Notch1. Expression of Hes1, Hes5 and Hesr has been shown to be sustained not only by Notch signaling but also by other signaling cues (Itoh et al, 2004;Nakashima et al, 2001;Sanalkumar et al, 2010;Timmerman et al, 2004).…”

Section: Expression Of Notch Target Genes Is Reduced In Mice Lacking mentioning

confidence: 99%

Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo

et al. 2011

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SUMMARYMastermind (Mam) is one of the elements of Notch signaling, a system that plays a pivotal role in metazoan development. Mam proteins form transcriptionally activating complexes with the intracellular domains of Notch, which are generated in response to the ligand-receptor interaction, and CSL DNA-binding proteins. In mammals, three structurally divergent Mam isoforms (MamL1, MamL2 and MamL3) have been identified. There have also been indications that Mam interacts functionally with various other transcription factors, including the p53 tumor suppressor, -catenin and NF-B. We have demonstrated previously that disruption of MamL1 causes partial deficiency of Notch signaling in vivo. However, MamL1-deficient mice did not recapitulate total loss of Notch signaling, suggesting that other members could compensate for the loss or that Notch signaling could proceed in the absence of Mam in certain contexts. Here, we report the generation of lines of mice null for MamL3. Although MamL3-null mice showed no apparent abnormalities, mice null for both MamL1 and MamL3 died during the early organogenic period with classic pan-Notch defects. Furthermore, expression of the lunatic fringe gene, which is strictly controlled by Notch signaling in the posterior presomitic mesoderm, was undetectable in this tissue of the double-null embryos. Neither of the single-null embryos exhibited any of these phenotypes. These various roles of the three Mam proteins could be due to their differential physical characteristics and/or their spatiotemporal distributions. These results indicate that engagement of Mam is essential for Notch signaling, and that the three Mam isoforms have distinct roles in vivo.

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Non-canonical activation of Notch signaling/target genes in vertebrates

Cited by 78 publications

References 105 publications

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

Notch signaling represses p63 expression in the developing surface ectoderm

Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo

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