The Murine Ortholog of <i>Notchless</i>, a Direct Regulator of the Notch Pathway in <i>Drosophila melanogaster</i>, Is Essential for Survival of Inner Cell Mass Cells

Cormier, Sarah; Bras, Stéphanie Le; Souilhol, Céline; Vandormael-Pournin, Sandrine; Durand, Béatrice; Babinet, Charles; Baldacci, Patricia; Cohen-Tannoudji, Michel

doi:10.1128/mcb.26.9.3541-3549.2006

Cited by 28 publications

(43 citation statements)

References 50 publications

(47 reference statements)

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“…We previously showed that Nle is widely expressed in the mouse. 24 To examine more precisely its pattern of expression in the adult small intestine, we performed RT-qPCR and western blot analyses on crypts and villi fractions. We found that both Nle mRNA and protein were enriched in crypts compared with villi ( Figures 1a and b).…”

Section: Resultsmentioning

confidence: 99%

“…56 Future investigations using the NleVilcKO model will help to obtain a deeper understanding on the mechanisms that link ribosomes biogenesis to intestinal cancer. 23 Nle null , 24 Villin-CreERT2, 57 Lgr5 GFP-IRES-CreERT2 , 58 p53 − . 59 To generate Control and NleVilcKO mice, Villin-CreERT2 tg/tg ; Nle flox/flox mice were crossed to Nle null/+ mice.…”

Section: Discussionmentioning

confidence: 99%

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Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

et al. 2015

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International audienceRibosome biogenesis is an essential cellular process. Its impairment is associated with developmental defects and increased risk of cancer. The in vivo cellular responses to defective ribosome biogenesis and the underlying molecular mechanisms are still incompletely understood. In particular, the consequences of impaired ribosome biogenesis within the intestinal epithelium in mammals have not been investigated so far. Here we adopted a genetic approach to investigate the role of Notchless (NLE), an essential actor of ribosome biogenesis, in the adult mouse intestinal lineage. Nle deficiency led to defects in the synthesis of large ribosomal subunit in crypts cells and resulted in the rapid elimination of intestinal stem cells and progenitors through distinct types of cellular responses, including apoptosis, cell cycle arrest and biased differentiation toward the goblet cell lineage. Similar observations were made using the rRNA transcription inhibitor CX-5461 on intestinal organoids culture. Importantly, we found that p53 activation was responsible for most of the cellular responses observed, including differentiation toward the goblet cell lineage. Moreover, we identify the goblet cell-specific marker Muc2 as a direct transcriptional target of p53. Nle-deficient ISCs and progenitors disappearance persisted in the absence of p53, underlying the existence of p53-independent cellular responses following defective ribosome biogenesis. Our data indicate that NLE is a crucial factor for intestinal homeostasis and provide new insights into how perturbations of ribosome biogenesis impact on cell fate decisions within the intestinal epithelium

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

et al. 2015

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“…Another explanation would be that the function of NLE/RSA4 and/or MDN1/REA1 may not be restricted to 60S subunit biogenesis, as was determined for other 60S trans-acting factors (Tschochner and Hurt, 2003). In animals, the NLE gene was shown to be involved in the regulation of the Notch receptor activity (Cormier et al, 2006;Royet et al, 1998). The phenotypic difference could also be attributable to the different nature of the transformed lines studied.…”

Section: Discussionmentioning

confidence: 97%

The MIDASIN and NOTCHLESS genes are essential for female gametophyte development in Arabidopsis thaliana

Chantha

Gray-Mitsumune

Houde

et al. 2010

Physiol Mol Biol Plants

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Female gametophyte development in Arabidopsis thaliana follows a well-defined program that involves many fundamental cellular processes. In this study, we report the involvement of the Arabidopsis thaliana MIDASIN1 (AtMDN1) gene during female gametogenesis through the phenotypic characterization of plants heterozygous for an insertional mdn1 mutant allele. The MDN1 yeast ortholog has previously been shown to encode a non-ribosomal protein involved in the maturation and assembly of the 60S ribosomal subunit. Heterozygous MDN1/mdn1 plants were semisterile and mdn1 allele transmission through the female gametophyte was severely affected. Development of mdn1 female gametophyte was considerably delayed compared to their wild-type siblings. However, delayed mdn1 female gametophytes were able to reach maturity and a delayed pollination experiment showed that a small proportion of the female gametophytes were functional. We also report that the Arabidopsis NOTCHLESS (AtNLE) gene is also required for female gametogenesis. The NLE protein has been previously shown to interact with MDN1 and to be also involved in 60S subunit biogenesis. The introduction of an AtNLE-RNA interference construct in Arabidopsis led to semisterility defects. Defective female gametophytes were mostly arrested at the one-nucleate (FG1) developmental stage. These data suggest that the activity of both AtMDN1 and AtNLE is essential for female gametogenesis progression.

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“…Furthermore, using a biochemical approach, it was demonstrated that Notchless binds to NICD (26). Similarly and importantly, we recently demonstrated that murine Nle protein has conserved its ability to modulate Notch activity (3). Therefore, the phenotypic consequences of disrupting mNle, the mouse ortholog of Notchless, namely, death of embryos shortly after implantation, were consistent with the notion that Notch signaling is implicated in very early development, in apparent contradiction to the delayed phenotypic consequences of Pofut1 or Rbpsuh disruption.…”

Section: Discussionmentioning

confidence: 99%

RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

Souilhol

Cormier

Tanigaki

et al. 2006

Molecular and Cellular Biology

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The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-J-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.

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The Murine Ortholog of Notchless, a Direct Regulator of the Notch Pathway in Drosophila melanogaster, Is Essential for Survival of Inner Cell Mass Cells

Cited by 28 publications

References 50 publications

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

The MIDASIN and NOTCHLESS genes are essential for female gametophyte development in Arabidopsis thaliana

RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

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