Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1673-1682 ◽  
Author(s):  
M. Gho ◽  
M. Lecourtois ◽  
G. Geraud ◽  
J.W. Posakony ◽  
F. Schweisguth
Keyword(s):  
Subcellular Localization ◽  
Cell Fate ◽  
Sense Organ ◽  
Wing Disc ◽  
Tissue Polarity ◽  
Cell Fate Decisions ◽  
Suppressor Of Hairless ◽  
Evolutionarily Conserved ◽  
Disc Cells ◽  
Sensory Organ Precursor

During imaginal development of Drosophila, Suppressor of Hairless [Su(H)], an evolutionarily conserved transcription factor that mediates intracellular signalling by the Notch (N) receptor, controls successive alternative cell fate decisions leading to the differentiation of multicellular sensory organs. We describe here the distribution of the Su(H) protein in the wing disc epithelium throughout development of adult sense organs. Su(H) was found to be evenly distributed in the nuclei of all imaginal disc cells during sensory organ precursor cells selection. Thus differential expression and/or subcellular localization of Su(H) is not essential for its function. Soon after division of the pIIa secondary precursor cell, Su(H) specifically accumulates in the nucleus of the future socket cell. At the onset of differentiation of the socket cell, Su(H) is also detected in the cytoplasm. In this differentiating cell, N and deltex participate in the cytoplasmic retention of Su(H). Still, Su(H) does not colocalize with N at the apical-lateral membranes. These observations suggest that N regulates in an indirect manner the cytoplasmic localization of Su(H) in the socket cell. Finally, the pIIb, shaft and socket cells are found to adopt invariant positions along the anteroposterior axis of the notum. This raises the possibility that tissue-polarity biases these N-mediated cell fate choices.

Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1433-1441 ◽  
Author(s):  
F. Schweisguth ◽  
J.W. Posakony
Keyword(s):  
Cell Fate ◽  
Imaginal Disc ◽  
Sensory Organ ◽  
Cell Fate Decisions ◽  
Suppressor Of Hairless ◽  
Disc Cells ◽  
Sensory Organ Precursor ◽  
Fate Decision ◽  
Mutant Phenotypes ◽  
Proneural Cluster

Successive alternative cell fate choices in the imaginal disc epithelium lead to the differentiation of a relatively invariant pattern of multicellular adult sensory organs in Drosophila. We show here that the activity of Suppressor of Hairless is required for both the sensory organ precursor (SOP) versus epidermal cell fate decision, and for the trichogen (shaft) versus tormogen (socket) cell fate choice. Complete loss of Suppressor of Hairless function causes most proneural cluster cells to accumulate high levels of the achaete and Delta proteins and to adopt the SOP fate. Late or partial reduction in Suppressor of Hairless activity leads to the apparent transformation of the tormogen (socket) cell into a second trichogen (shaft) cell, producing a ‘double shaft’ phenotype. We find that overexpression of Suppressor of Hairless has the opposite phenotypic effects. SOP determination is prevented by an early excess of Suppressor of Hairless activity, while at a later stage, the trichogen (shaft) cell is transformed into a second tormogen (socket) cell, resulting in ‘double socket’ bristles. We conclude that, for two different cell fate decisions in adult sensory organ development, decreasing or increasing the level of Suppressor of Hairless function confers mutant phenotypes that closely resemble those associated with gain and loss of Hairless activity, respectively. These results, along with the intermediate SOP phenotype observed in Suppressor of Hairless; Hairless double mutant imaginal discs, suggest that the two genes act antagonistically to commit imaginal disc cells stably to alternative fates.

scholarly journals Metabolic Control of m6A RNA Modification

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 80
Author(s):  
Joohwan Kim ◽  
Gina Lee
Keyword(s):  
Cell Fate ◽  
Metabolic Pathways ◽  
Epigenetic Modification ◽  
Genetic Material ◽  
Rna Modification ◽  
Cell Fate Decisions ◽  
Disease States ◽  
Evolutionarily Conserved ◽  
Regulate Cell Growth ◽  
Epigenetic Processes

Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved RNA modification. It functions in various aspects of developmental and disease states, by controlling RNA metabolism, such as stability and translation. Similar to other epigenetic processes, m6A modification is regulated by specific enzymes, including writers (methyltransferases), erasers (demethylases), and readers (m6A-binding proteins). As this is a reversible enzymatic process, metabolites can directly influence the flux of this reaction by serving as substrates and/or allosteric regulators. In this review, we will discuss recent understanding of the regulation of m6A RNA modification by metabolites, nutrients, and cellular metabolic pathways.

Role of Notch and achaete-scute complex in the expression of Enhancer of split bHLH proteins

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3745-3752 ◽  
Author(s):  
V. Jennings ◽  
J. de Celis ◽  
C. Delidakis ◽  
A. Preiss ◽  
S. Bray
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Interaction Mechanism ◽  
Cell Interaction ◽  
Precursor Cell ◽  
Notch Receptor ◽  
Sensory Organ ◽  
Cell Fate Decisions ◽  
Sensory Organ Precursor ◽  
Enhancer Of Split

The proteins encoded by Notch and the Enhancer of split complex are components of a cell-cell interaction mechanism which is important in many cell fate decisions throughout development. One such decision is the formation of the sensory organ precursor cell during the development of the peripheral nervous system in Drosophila. Cells acquire the potential to be neural through the expression of the proneural genes, and the Notch pathway is required to limit neural fate to a single cell from a proneural cluster. However, despite extensive analysis, the precise pathways linking the proneural with Notch and Enhancer of split gene functions remain obscure. For example, it has been suggested that achaete-scute complex proteins directly activate Enhancer of split genes leaving the action of Notch in the pathway unclear. Using monoclonal antibodies that recognise products of the Enhancer of split complex, we show that these proteins accumulate in the cells surrounding the developing sensory organ precursor cell and that their expression is dependent on the activity of Notch and does not directly correlate with expression of Achaete. We further clarify the pathway by showing that ubiquitous expression of an activated Notch receptor leads to widespread accumulation of Enhancer of split proteins even in the absence of achaete-scute complex proteins. Thus Enhancer of split protein expression in response to Notch activity does not require achaete-scute complex proteins.

scholarly journals Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

2015 ◽  
Vol 309 (8) ◽  
pp. C511-C521 ◽  
Author(s):  
Laura Novellasdemunt ◽  
Pedro Antas ◽  
Vivian S. W. Li
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Wnt Pathway ◽  
High Throughput Sequencing ◽  
Wnt Signaling Pathway ◽  
Negative Regulator ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Evolutionarily Conserved

The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development and tissue homeostasis. Notably, comprehensive genetic studies in Drosophila and mice in the past decades have demonstrated the crucial role of Wnt signaling in intestinal stem cell maintenance by regulating proliferation, differentiation, and cell-fate decisions. Wnt signaling has also been implicated in a variety of cancers and other diseases. Loss of the Wnt pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of human colorectal cancers (CRC). Recent advances in high-throughput sequencing further reveal many novel recurrent Wnt pathway mutations in addition to the well-characterized APC and β-catenin mutations in CRC. Despite attractive strategies to develop drugs for Wnt signaling, major hurdles in therapeutic intervention of the pathway persist. Here we discuss the Wnt-activating mechanisms in CRC and review the current advances and challenges in drug discovery.

scholarly journals GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate

2020 ◽  
Author(s):  
Mengyi Song ◽  
Xuefei Yuan ◽  
Claudia Racioppi ◽  
Meaghan Leslie ◽  
Anastasiia Aleksandrova ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Heart Development ◽  
Gene Expression Analysis ◽  
Cell Fate Decisions ◽  
Evolutionarily Conserved ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Cardiac Mesoderm ◽  
Invertebrate Chordate

AbstractGATA4/5/6 transcription factors play essential, conserved roles in heart development. How these factors mediate the transition from multipotent mesoderm progenitors to a committed cardiac fate is unclear. To understand how GATA4/5/6 modulate cell fate decisions we labelled, isolated, and performed single-cell gene expression analysis on cells that express gata5 at pre-cardiac time points spanning gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was dramatically altered. In addition to the expected absence of cardiac mesoderm, we observed a concomitant expansion of cranial-pharyngeal mesoderm. Functional genetic analyses in zebrafish and the invertebrate chordate Ciona, which possess a single GATA4/5/6 homolog, revealed an essential and cell-autonomous role for GATA4/5/6 in promoting cardiac and inhibiting pharyngeal mesoderm identity. Overall, the maintenance and repression of GATA4/5/6 activity plays a critical, evolutionarily conserved role in early development.

scholarly journals An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

Development ◽  
2020 ◽  
Vol 147 (20) ◽  
pp. dev187856
Author(s):  
Veena Kinare ◽  
Archana Iyer ◽  
Hari Padmanabhan ◽  
Geeta Godbole ◽  
Tooba Khan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regional Identity ◽  
Wing Disc ◽  
Cell Fate Specification ◽  
Dimerization Domain ◽  
Molecular Identity ◽  
Evolutionarily Conserved ◽  
Chimeric Construct ◽  
Single Transcript ◽  
Tetrameric Complex

ABSTRACTThe protein co-factor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain.

scholarly journals An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

2020 ◽  
Author(s):  
Veena Kinare ◽  
Archana Iyer ◽  
Hari Padmanabhan ◽  
Geeta Godbole ◽  
Tooba Khan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regional Identity ◽  
Wing Disc ◽  
Dimerization Domain ◽  
Evolutionarily Conserved ◽  
Chimeric Construct ◽  
Summary Statement ◽  
Hippocampal Development ◽  
Single Transcript ◽  
Tetrameric Complex

AbstractProtein cofactor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain.Summary statementSimilar to an Apterous-Chip mechanism that patterns the Drosophila wing blade, interaction between mammalian orthologs Lhx2 and Ldb1 regulates multiple aspects of hippocampal development in the mouse.

scholarly journals Unique functions for Notch4 in murine embryonic lymphangiogenesis

Angiogenesis ◽  
2021 ◽  
Author(s):  
Ajit Muley ◽  
Minji Kim Uh ◽  
Glicella Salazar-De Simone ◽  
Bhairavi Swaminathan ◽  
Jennifer M. James ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Dominant Role ◽  
Dominant Negative ◽  
Cell Fate Decisions ◽  
Dominant Negative Form ◽  
Evolutionarily Conserved ◽  
Lymphatic Development ◽  
Lymphatic Density ◽  
Negative Form

AbstractIn mice, embryonic dermal lymphatic development is well understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Actively growing embryonic dermal lymphatics expressed NOTCH1, NOTCH4, and DLL4 which correlated with Notch activity. In lymphatic endothelial cells (LECs), DLL4 activation of Notch induced a subset of Notch effectors and lymphatic genes, which were distinctly regulated by Notch1 and Notch4 activation. Treatment of LECs with VEGF-A or VEGF-C upregulated Dll4 transcripts and differentially and temporally regulated the expression of Notch1 and Hes/Hey genes. Mice nullizygous for Notch4 had an increase in the closure of the lymphangiogenic fronts which correlated with reduced vessel caliber in the maturing lymphatic plexus at E14.5 and reduced branching at E16.5. Activation of Notch4 suppressed LEC migration in a wounding assay significantly more than Notch1, suggesting a dominant role for Notch4 in regulating LEC migration. Unlike Notch4 nulls, inhibition of canonical Notch signaling by expressing a dominant negative form of MAML1 (DNMAML) in Prox1+ LECs led to increased lymphatic density consistent with an increase in LEC proliferation, described for the loss of LEC Notch1. Moreover, loss of Notch4 did not affect LEC canonical Notch signaling. Thus, we propose that Notch4 signaling and canonical Notch signaling have distinct functions in the coordination of embryonic dermal lymphangiogenesis.

scholarly journals Bazooka/Par3 cooperates with Sanpodo for the assembly of Notch signaling clusters following asymmetric division of Drosophila sensory organ precursor cells

2021 ◽  
Author(s):  
Elise Houssin ◽  
Mathieu Pinot ◽  
Karen Bellec ◽  
Roland Le Borgne
Keyword(s):  
Plasma Membrane ◽  
Notch Signaling ◽  
Cell Fate ◽  
Sensory Organ ◽  
Cell Fate Decisions ◽  
Daughter Cells ◽  
Delta Activity ◽  
Multiple Cell ◽  
Sensory Organ Precursor ◽  
Fate Decision

SummaryIn multiple cell lineages, Delta-Notch signaling regulates cell fate decisions owing to unidirectional signaling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localize apically and basally at the pIIa-pIIb interface, are expressed at low levels and their residence time at the plasma membrane is in the order of the minute. How Delta can effectively interact with Notch to trigger signaling from a large plasma membrane remains poorly understood. Here, we report that the signaling interface possesses a unique apicobasal polarity with Par3/Bazooka localizing in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface where it co-clusters with Bazooka and the Notch cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities, are also positive for Neuralized, the E3 ligase required for Delta-activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signaling.

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