scholarly journals Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ignacio Medina-Yáñez ◽  
Gonzalo H. Olivares ◽  
Franco Vega-Macaya ◽  
Marek Mlodzik ◽  
Patricio Olguín
Keyword(s):  
Phosphatidic Acid ◽  
Cell Fate ◽  
Phospholipase D ◽  
Membrane Lipids ◽  
Adaptor Protein ◽  
Notch Signalling ◽  
Α Subunit ◽  
Asymmetric Cell Divisions ◽  
Cell Fate Decisions ◽  
Cell Divisions

AbstractOrgan cell diversity depends on binary cell-fate decisions mediated by the Notch signalling pathway during development and tissue homeostasis. A clear example is the series of binary cell-fate decisions that take place during asymmetric cell divisions that give rise to the sensory organs of Drosophila melanogaster. The regulated trafficking of Sanpodo, a transmembrane protein that potentiates receptor activity, plays a pivotal role in this process. Membrane lipids can regulate many signalling pathways by affecting receptor and ligand trafficking. It remains unknown, however, whether phosphatidic acid regulates Notch-mediated binary cell-fate decisions during asymmetric cell divisions, and what are the cellular mechanisms involved. Here we show that increased phosphatidic acid derived from Phospholipase D leads to defects in binary cell-fate decisions that are compatible with ectopic Notch activation in precursor cells, where it is normally inactive. Null mutants of numb or the α-subunit of Adaptor Protein complex-2 enhance dominantly this phenotype while removing a copy of Notch or sanpodo suppresses it. In vivo analyses show that Sanpodo localization decreases at acidic compartments, associated with increased internalization of Notch. We propose that Phospholipase D-derived phosphatidic acid promotes ectopic Notch signalling by increasing receptor endocytosis and inhibiting Sanpodo trafficking towards acidic endosomes.

Conservation of the Notch signalling pathway in mammalian neurogenesis

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1139-1148 ◽  
Author(s):  
J.L. Pompa de la ◽  
A. Wakeham ◽  
K.M. Correia ◽  
E. Samper ◽  
S. Brown ◽  
...  
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Stem Cell Differentiation ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Notch Signalling Pathway ◽  
Altered Expression ◽  
Cell Fate Decisions ◽  
Targeted Mutation ◽  
Multiple Cell

The Notch pathway functions in multiple cell fate determination processes in invertebrate embryos, including the decision between the neuroblast and epidermoblast lineages in Drosophila. In the mouse, targeted mutation of the Notch pathway genes Notch1 and RBP-Jk has demonstrated a role for these genes in somite segmentation, but a function in neurogenesis and in cell fate decisions has not been shown. Here we show that these mutations lead to altered expression of the Notch signalling pathway homologues Hes-5, Mash-1 and Dll1, resulting in enhanced neurogenesis. Precocious neuronal differentiation is indicated by the expanded expression domains of Math4A, neuroD and NSCL-1. The RBP-Jk mutation has stronger effects on expression of these genes than does the Notch1 mutation, consistent with functional redundancy of Notch genes in neurogenesis. Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation.

Dynamics of Notch signalling in the mouse oviduct and uterus during the oestrous cycle

2016 ◽  
Vol 28 (11) ◽  
pp. 1663 ◽  
Author(s):  
D. Murta ◽  
M. Batista ◽  
A. Trindade ◽  
E. Silva ◽  
L. Mateus ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Fate ◽  
Expression Patterns ◽  
Cell Signalling ◽  
Notch Signalling ◽  
Notch Receptor ◽  
Effector Proteins ◽  
Oestrous Cycle ◽  
Cell Fate Decisions ◽  
Effector Genes

The oviduct and uterus undergo extensive cellular remodelling during the oestrous cycle, requiring finely tuned intercellular communication. Notch is an evolutionarily conserved cell signalling pathway implicated in cell fate decisions in several tissues. In the present study we evaluated the quantitative real-time polymerase chain reaction (real-time qPCR) and expression (immunohistochemistry) patterns of Notch components (Notch1–4, Delta-like 1 (Dll1), Delta-like 4 (Dll4), Jagged1–2) and effector (hairy/enhancer of split (Hes) 1–2, Hes5 and Notch-Regulated Ankyrin Repeat-Containing Protein (Nrarp)) genes in the mouse oviduct and uterus throughout the oestrous cycle. Notch genes are differentially transcribed and expressed in the mouse oviduct and uterus throughout the oestrous cycle. The correlated transcription levels of Notch components and effector genes, and the nuclear detection of Notch effector proteins, indicate that Notch signalling is active. The correlation between transcription levels of Notch genes and progesterone concentrations, and the association between expression of Notch proteins and progesterone receptor (PR) activation, indicate direct progesterone regulation of Notch signalling. The expression patterns of Notch proteins are spatially and temporally specific, resulting in unique expression combinations of Notch receptor, ligand and effector genes in the oviduct luminal epithelium, uterus luminal and glandular epithelia and uterine stroma throughout the oestrous cycle. Together, the results of the present study imply a regulatory role for Notch signalling in oviduct and uterine cellular remodelling occurring throughout the oestrous cycle.

scholarly journals Quantitative and dynamic cell polarity tracking in plant cells

2020 ◽  
Author(s):  
Yan Gong ◽  
Rachel Varnau ◽  
Eva-Sophie Wallner ◽  
Dominique C. Bergmann ◽  
Lily S. Cheung
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Brachypodium Distachyon ◽  
Quantitative Information ◽  
Tissue Level ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Versatile Tool ◽  
Dynamic Cell ◽  
Microscopy Techniques

ABSTRACTQuantitative information on the spatiotemporal distribution of polarized proteins is central for understanding cell-fate determination, yet collecting sufficient data for statistical analysis is difficult to accomplish with manual measurements. Here we present POME, a semi-automated pipeline for the quantification of cell polarity, and demonstrate its application to a variety of developmental contexts. POME analysis reveals that during asymmetric cell divisions in the Arabidopsis thaliana stomatal lineage, polarity proteins BASL and BRXL2 are more asynchronous and less mutually dependent than previously thought. While their interaction is important to maintain their polar localization and recruit other effectors to regulate asymmetric cell divisions, BRXL2 polarization precedes that of BASL and can be initiated in BASL’s absence. Uncoupling of polarization from BASL activity is also seen in Brachypodium distachyon, where we find that the MAPKKK BdYDA1 is segregated and polarized following asymmetric division. Our results demonstrate that POME is a versatile tool, which by itself or combined with tissue-level studies and advanced microscopy techniques can help uncover new mechanisms of cell polarity.

rZIP, a RING-leucine zipper protein that regulates cell fate determination during Dictyostelium development

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1203-1213 ◽  
Author(s):  
P. Balint-Kurti ◽  
G. Ginsburg ◽  
O. Rivero-Lezcano ◽  
A.R. Kimmel
Keyword(s):  
Cell Fate ◽  
Leucine Zipper ◽  
Phosphorylation Site ◽  
Adaptor Protein ◽  
Specific Gene ◽  
Cell Fate Decisions ◽  
Cellular Aggregation ◽  
Constitutive Overexpression ◽  
Zinc Binding Domain

rZIP is an approx. 32 kDa, multi-domain protein of Dictyostelium discoideum whose structural motifs include a RING (zinc-binding) domain, a leucine zipper, a glutamine repeat, an SH3-binding region and a consensus phosphorylation site for MAP kinase. In vitro, rZIP forms homodimers and interacts specifically with the SH3 domain(s) of the Nck adaptor protein. rZIP is expressed maximally during cell differentiation at approximately equivalent levels in all cells. Disruption of the rZIP gene rzpA results in altered cellular aggregation, impaired slug migration, and aberrant patterning of prespore and prestalk cells, the major progenitor classes. In rzpA- strains, prespore-specific genes are overexpressed and prestalk expression zones are reduced. Conversely, constitutive overexpression of rzpA markedly decreases prespore-specific gene expression and significantly increases the expression of prestalk-specific genes. Further, induced transdifferentiation of prespore cells into prestalk cells is inhibited in rzpA-slugs. In light of these patterning defects, we suggest that the RING/zipper protein rZIP plays an important role in early cell fate decisions in Dictyostelium, acting as a positive regulator of prestalk differentiation and an inhibitor of prespore differentiation.

scholarly journals Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

2015 ◽  
Vol 211 (4) ◽  
pp. 737-739 ◽  
Author(s):  
Marisa M. Faraldo ◽  
Marina A. Glukhova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Asymmetric Cell Divisions ◽  
Stem Cell Expansion ◽  
Cell Divisions ◽  
Cell Fate Determinant ◽  
Mammary Stem

In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny.

scholarly journals Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions

Development ◽  
2010 ◽  
Vol 137 (15) ◽  
pp. 2527-2537 ◽  
Author(s):  
M. Yamamoto ◽  
R. Morita ◽  
T. Mizoguchi ◽  
H. Matsuo ◽  
M. Isoda ◽  
...  
Keyword(s):  
Cell Fate ◽  
Notch Signalling ◽  
Cell Fate Decisions

scholarly journals A Plant-Specific Polarity Module Establishes Cell Fate Asymmetry in the Arabidopsis Stomatal Lineage

2019 ◽  
Author(s):  
Matthew H. Rowe ◽  
Juan Dong ◽  
Annika K. Weimer ◽  
Dominique C. Bergmann
Keyword(s):  
Genetic Diversity ◽  
Cell Fate ◽  
Cell Polarity ◽  
Asymmetric Cell Division ◽  
Diverse Range ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Collective Activity ◽  
Developmental Contexts ◽  
Stomatal Lineage

SUMMARYGenerating cell polarity in anticipation of asymmetric cell division is required in many developmental contexts across a diverse range of species. Physical and genetic diversity among major multicellular taxa, however, demand different molecular solutions to this problem. The Arabidopsis stomatal lineage displays asymmetric, stem cell-like and oriented cell divisions, which require the activity of the polarly localized protein, BASL. Here we identify the plant-specific BREVIS RADIX (BRX) family as localization and activity partners of BASL. We show that members of the BRX family are polarly localized to peripheral domains in stomatal lineage cells and that their collective activity is required for asymmetric cell divisions. We further demonstrate a mechanism for these behaviors by uncovering mutual, yet unequal dependencies of BASL and the BRX family for each other’s localization and segregation at the periphery of stomatal lineage cells.

SUMOylated Non-canonical Polycomb PRC1.6 Complex as a Prerequisite for Recruitment of Transcription Factor RBPJ

2021 ◽  
Author(s):  
Małgorzata Sotomska ◽  
Robert Liefke ◽  
Francesca Ferrante ◽  
Heiko Schwederski ◽  
Franz Oswald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Target Gene ◽  
Target Genes ◽  
Adult Stem Cell ◽  
Notch Signalling ◽  
Cell Fate Decisions ◽  
Contact Points ◽  
Coactivator Complex

Abstract BackgroundNotch signaling controls cell fate decisions in many contexts during development and adult stem cell homeostasis and, when dysregulated, leads to carcinogenesis. The central transcription factor RBPJ assembles the Notch coactivator complex in the presence of Notch signalling, and represses Notch target gene expression in its absence.ResultsWe identified L3MBTL2 and additional members of the non-canonical polycomb repressive PRC1.6 complex in DNA-bound RBPJ associated complexes and demonstrate that L3MBTL2 directly interacts with RBPJ. Depletion of RBPJ does not affect occupancy of PRC1.6 components at Notch target genes. Conversely, absence of L3MBTL2 reduces RBPJ occupancy at enhancers of Notch target genes. Since L3MBTL2 and additional members of the PRC1.6 are known to be SUMOylated, we investigated whether RBPJ uses SUMO-moieties as contact points. Indeed, we found that RBPJ binds to SUMO2/3 and that this interaction depends on a defined SUMO-interaction motif. Furthermore, we show that pharmacological inhibition of SUMOylation reduces RBPJ occupancy at Notch target genes.ConclusionsWe propose that the PRC1.6 complex and its conjugated SUMO-modifications provide a scaffold that is recognized by RBPJ and promotes its recruitment to Notch target genes.

scholarly journals Conservation and Divergence of YODA MAPKKK Function in Regulation of Grass Epidermal Patterning

2018 ◽  
Author(s):  
Emily Abrash ◽  
M Ximena Anleu Gil ◽  
Juliana L Matos ◽  
Dominique C Bergmann
Keyword(s):  
Cell Fate ◽  
Cell Types ◽  
Lineage Tracing ◽  
Cell Fates ◽  
Kinase Gene ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Asymmetric Divisions ◽  
Species Specific ◽  
Multicellular Organisms

AbstractAll multicellular organisms must properly pattern cell types to generate functional tissues and organs. The organized and predictable cell lineages of the Brachypodium leaf enabled us to characterize the role of the MAPK kinase kinase gene BdYODA1 in regulating asymmetric cell divisions. We find that YODA genes promote normal stomatal spacing patterns in both Arabidopsis and Brachypodium, despite species-specific differences in those patterns. Using lineage tracing and cell fate markers, we show that, unexpectedly, patterning defects in bdyoda1 mutants do not arise from faulty physical asymmetry in cell divisions but rather from improper enforcement of alternative cellular fates after division. These cross-species comparisons allow us to refine our interpretations of MAPK activities during plant asymmetric cell divisions.Summary StatementAnalysis of Brachypodium leaf epidermis development reveals that the MAPKKK, BdYODA1, regulates asymmetric divisions by enforcing resultant cell fates rather than driving initial physical asymmetries.

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