Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo

Geffers, Insa; Serth, Katrin; Chapman, Gavin; Jaekel, Robert; Schuster-Gossler, Karin; Cordes, Ralf; Sparrow, Duncan B.; Kremmer, Elisabeth; Dunwoodie, Sally L.; Klein, Thomas; Gossler, Achim

doi:10.1084/jem2048oia20

Cited by 33 publications

(58 citation statements)

References 24 publications

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“…We performed similar experiments to examine whether the function of Jag1 and Dll3 depends on Rumi, but were not able to reach a conclusion, because these two mammalian ligands did not induce Notch signaling in wild-type or Rumi -/-clones in Drosophila using this assay (see Fig. S5 in the supplementary material), in agreement with a previous report on Dll3 (Geffers et al, 2007). These data suggest that Oglucosylation by Rumi is not essential for the function of the rat Dll1.…”

Section: Research Articlesupporting

confidence: 76%

“…UAS-ratDLL1-HA, UAS-mDLL3-FLAG (Geffers et al, 2007) and UAS-attB-ratJagged1 (this study) were used to overexpress mammalian ligands in mitotic clones of the null allele rumi D26 (Acar et al, 2008) or in mitotic clones of a wild-type chromosome (control) by using the MARCM technique (Lee and Luo, 2001) as described previously (Acar et al, 2008). Wing imaginal discs were dissected and fixed by using standard protocols and stained with a-Jag1 (1:100, Santa Cruz Biotechnology), a-Cut (1:500, DSHB) and/or a-FLAG (1:500, Sigma) antibodies.…”

Section: Transgenic Fly Experimentsmentioning

confidence: 99%

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Regulation of mammalian Notch signaling and embryonic development by the proteinO-glucosyltransferase Rumi

et al. 2011

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Section: Research Articlesupporting

confidence: 76%

Section: Transgenic Fly Experimentsmentioning

confidence: 99%

Regulation of mammalian Notch signaling and embryonic development by the proteinO-glucosyltransferase Rumi

et al. 2011

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“…This may reflect a requirement for Dll3 expression in the anterior PSM during secondary body formation. Alternatively, it was recently shown that the loss of Dll3 in the PSM leads to a loss or reduction in NICD levels in region I of the PSM, in contrast to the ubiquitous Notch1 activation observed in Lfng ⌬FCE1/⌬FCE1 embryos (Geffers et al, 2007). This raises the possibility that while oscillatory Notch1 activation in the posterior PSM is not required during secondary body formation, some level of Notch1 activation is still necessary during this process.…”

Section: Dll3-null Embryos Exhibit Similar Lfng Expression Patterns Tmentioning

confidence: 98%

Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton

et al. 2008

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The Notch pathway plays multiple roles during vertebrate somitogenesis, functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfng expression within the segmentation clock, but that maintains expression during R/C somite patterning (Lfng ⌬FCE1). In the absence of oscillatory Lfng expression, Notch activation is ubiquitous in the PSM of Lfng ⌬FCE1 embryos. Lfng ⌬FCE1 mice exhibit severe segmentation phenotypes in the thoracic and lumbar skeleton. However, the sacral and tail vertebrae are only minimally affected in Lfng ⌬FCE1 mice, suggesting that oscillatory Lfng expression and cyclic Notch activation are important in the segmentation of the thoracic and lumbar axial skeleton (primary body formation), but are largely dispensable for the development of sacral and tail vertebrae (secondary body formation). Furthermore, we find that the loss of cyclic Lfng has distinct effects on the expression of other clock genes during these two stages of development. Finally, we find that Lfng ⌬FCE1 embryos undergo relatively normal R/C somite patterning, confirming that Lfng roles in the segmentation clock are distinct from its functions in somite patterning. These results suggest that the segmentation clock may employ varied regulatory mechanisms during distinct stages of anterior/posterior axis development, and uncover previously unappreciated connections between the segmentation clock, and the processes of primary and secondary body formation.

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“…These results raise an interesting possibility that different Delta-like genes may sort out different subpopulations, or mark different steps in the transition from multipotency to neurogenic dividing progenitors in the retina. In this regard, it is interesting that occasional Dll3 expressing cells were not labeled with progenitor markers (PCNA); Dll3 is not able to activate Notch signaling, and may even attenuate Notch signaling levels (Ladi et al, 2005;Geffers et al, 2007). These data suggest that Dll3 may be involved in the terminal neurogenic step of progenitor differentiation.…”

Section: Mouse Retinal Progenitor Cells Express Delta-like Genesmentioning

confidence: 99%

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

Nelson

Hartman

Ray

et al. 2009

Developmental Dynamics

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SummaryDelta gene expression in Drosophila is regulated by proneural bHLH transcription factors, such as acheate-scute. In vertebrates, multiple Delta-like and proneural bHLH genes are expressed during neurogenesis, especially in the retina. We recently uncovered a relationship between Acheatescute like 1 (Ascl1), Delta-like genes, and Notch in chick retinal progenitors. Here, we report that mammalian retinal progenitors are also the primary source of Delta-like genes, likely signaling through Notch among themselves, while differentiating neurons expressed Jagged2. Ascl1 is coexpressed in Delta-like and Notch active progenitors, and required for normal Delta-like gene expression and Notch signaling. We also reveal a role for Ascl1 in the regulation of Hes6, a proneurogenic factor that inhibits Notch signaling to promote neural rather than glial differentiation. Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1 deficient retina.

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Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo

Cited by 33 publications

References 24 publications

Regulation of mammalian Notch signaling and embryonic development by the proteinO-glucosyltransferase Rumi

Regulation of mammalian Notch signaling and embryonic development by the proteinO-glucosyltransferase Rumi

Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

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