scholarly journals Regulation of Numb during planar cell polarity establishment in the Drosophila eye

2019 ◽  
Author(s):  
Pedro M Domingos ◽  
Andreas Jenny ◽  
David del Alamo ◽  
Marek Mlodzik ◽  
Hermann Steller ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Photoreceptor Cells ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Loss Of Function ◽  
Giant Larva ◽  
Signaling Activation

ABSTRACTThe establishment of planar cell polarity (PCP) in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells, determined by a Frizzled mediated signaling event that specifies R3 and induces Delta to activate Notch signaling in the neighboring cell, specifying it as R4. Here, we investigated the role of the Notch signaling negative regulator Numb in the specification of R3/R4 fates and PCP establishment in the Drosophila eye. We observed that Numb is transiently upregulated in R3 at the time of R3/R4 specification. This regulation of Numb levels in developing photoreceptors occurs at the post-transcriptional level and is dependent on Dishevelled, an effector of Frizzled signaling, and Lethal Giant Larva. We detected PCP defects in cells homozygous for numb15, but these defects were due to a loss of function mutation in fat (fatQ805*) being present in the numb15 chromosome. However, mosaic overexpression of Numb in R4 precursors (only) caused PCP defects and numb loss-of-function had a modifying effect on the defects found in a hypomorphic dishevelled mutation. Our results suggest that Numb levels are upregulated to reinforce the bias of Notch signaling activation in the R3/R4 pair, two post-mitotic cells that are not specified by asymmetric cell division.

scholarly journals The E3 Ubiquitin Ligase Mindbomb1 controls zebrafish Planar Cell Polarity

2021 ◽  
Author(s):  
Vishnu Muraleedharan Saraswathy ◽  
Priyanka Sharma ◽  
Akshai Janardhana Kurup ◽  
Sophie Polès ◽  
Morgane Poulain ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Polarity ◽  
Ubiquitin Ligase ◽  
Protein Trafficking ◽  
Planar Cell Polarity ◽  
E3 Ubiquitin Ligase ◽  
Notch Pathway ◽  
Ring Finger ◽  
Critical Event ◽  
Loss Of Function

Vertebrate Delta/Notch signaling involves multiple ligands, receptors and transcription factors. Delta endocytosis – a critical event for Notch activation – is however essentially controlled by the E3 Ubiquitin ligase Mindbomb1 (Mib1). Due to its position at a molecular bottleneck of the pathway, Mib1 inactivation is often used to inhibit Notch signaling. However, recent findings indicate that the importance of Mib1 extends beyond the Notch pathway. We report an essential role of Mib1 in Planar Cell Polarity (PCP). mib1 null mutants or morphants display impaired gastrulation stage Convergence Extension (CE) movements. Comparison of different mib1 mutants and functional rescue experiments indicate that Mib1 controls CE independently of Notch. In contrast, Mib1-dependent CE defects can be rescued using the PCP downstream mediator RhoA. Mib1 regulates CE through the RING Finger domains that have been implicated in substrate ubiquitination, suggesting that Mib1 may control PCP protein trafficking. Accordingly, we show that Mib1 controls the endocytosis of the PCP component Ryk and that Ryk internalization is required for CE. Numerous morphogenetic processes involve both Notch and PCP signaling. We show that Mib1, a known Notch signaling regulator, is also an essential PCP pathway component. Care should therefore be taken when interpreting Mib1 loss of function phenotypes.

scholarly journals Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yildiz Koca ◽  
Benjamin E. Housden ◽  
William J. Gault ◽  
Sarah J. Bray ◽  
Marek Mlodzik
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Planar Cell Polarity ◽  
Egf Receptor ◽  
Control Cell ◽  
Loss Of Function ◽  
Egfr Signaling ◽  
Specific Expression ◽  
Egfr Signaling Pathway ◽  
Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

Cortical Cyclin A controls spindle orientation during asymmetric cell division

2021 ◽  
Author(s):  
Pénélope Darnat ◽  
Angelique Burg ◽  
Jérémy Sallé ◽  
Jérôme Lacoste ◽  
Sophie Louvet-Vallée ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Cyclin A ◽  
Spindle Orientation ◽  
Posterior Cortex ◽  
Cell Diversity

Abstract Cell proliferation and cell polarity need to be precisely coordinated to orient the asymmetric cell divisions crucial for generating cell diversity in epithelia. In many instances, the Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is spatially and temporally coordinated with cell cycle progression has remained elusive. Using Drosophila sensory organ precursor cells as a model system, we show that Cyclin A, the main Cyclin driving the transition to M-phase of the cell cycle, is recruited to the apical-posterior cortex in prophase by the Frizzled/Dishevelled complex. This cortically localized Cyclin A then regulates the orientation of the division by recruiting Mud, a homologue of NuMA, the well-known spindle-associated protein. The observed non-canonical subcellular localization of Cyclin A reveals this mitotic factor as a direct link between cell proliferation, cell polarity and spindle orientation.

scholarly journals MKP-3 Has Essential Roles as a Negative Regulator of the Ras/Mitogen-Activated Protein Kinase Pathway during Drosophila Development

2004 ◽  
Vol 24 (2) ◽  
pp. 573-583 ◽  
Author(s):  
Myungjin Kim ◽  
Guang-Ho Cha ◽  
Sunhong Kim ◽  
Jun Hee Lee ◽  
Jeehye Park ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Fate ◽  
Photoreceptor Cells ◽  
Mapk Signaling ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Loss Of Function ◽  
Wing Vein ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) is a well-known negative regulator in the Ras/extracellular signal-regulated kinase (ERK)-MAPK signaling pathway responsible for cell fate determination and proliferation during development. However, the physiological roles of MKP-3 and the mechanism by which MKP-3 regulates Ras/Drosophila ERK (DERK) signaling in vivo have not been determined. Here, we demonstrated that Drosophila MKP-3 (DMKP-3) is critically involved in cell differentiation, proliferation, and gene expression by suppressing the Ras/DERK pathway, specifically binding to DERK via the N-terminal ERK-binding domain of DMKP-3. Overexpression of DMKP-3 reduced the number of photoreceptor cells and inhibited wing vein differentiation. Conversely, DMKP-3 hypomorphic mutants exhibited extra photoreceptor cells and wing veins, and its null mutants showed striking phenotypes, such as embryonic lethality and severe defects in oogenesis. All of these phenotypes were highly similar to those of the gain-of-function mutants of DERK/rl. The functional interaction between DMKP-3 and the Ras/DERK pathway was further confirmed by genetic interactions between DMKP-3 loss-of-function mutants or overexpressing transgenic flies and various mutants of the Ras/DERK pathway. Collectively, these data provide the direct evidences that DMKP-3 is indispensable to the regulation of DERK signaling activity during Drosophila development.

scholarly journals Meru couples planar cell polarity with apical-basal polarity during asymmetric cell division

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jennifer J Banerjee ◽  
Birgit L Aerne ◽  
Maxine V Holder ◽  
Simon Hauri ◽  
Matthias Gstaiger ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Building Blocks ◽  
Posterior Cortex ◽  
Daughter Cells ◽  
The Core ◽  
Cell Tissue ◽  
Specific Factors ◽  
Polarity Factor

Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation. In Drosophila sensory organ precursors (SOPs), the core PCP components initiate the planar polarization of apical-basal determinants, ensuring asymmetric division into daughter cells of different fates. We show that Meru, a RASSF9/RASSF10 homologue, is expressed specifically in SOPs, recruited to the posterior cortex by Frizzled/Dishevelled, and in turn polarizes the apical-basal polarity factor Bazooka (Par3). Thus, Meru belongs to a class of proteins that act cell/tissue-specifically to remodel the core polarity machinery.

scholarly journals Integrins are required for synchronous ommatidial rotation in the Drosophila eye linking planar cell polarity signalling to the extracellular matrix

Open Biology ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 190148 ◽  
Author(s):  
Maria Thuveson ◽  
Konstantin Gaengel ◽  
Giovanna M. Collu ◽  
Mei-ling Chin ◽  
Jaskirat Singh ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Rho Kinase ◽  
Cell Movement ◽  
Interaction Network ◽  
Loss Of Function ◽  
Ommatidial Rotation ◽  
Cytoskeletal Elements ◽  
Function Activity

Integrins mediate the anchorage between cells and their environment, the extracellular matrix (ECM), and form transmembrane links between the ECM and the cytoskeleton, a conserved feature throughout development and morphogenesis of epithelial organs. Here, we demonstrate that integrins and components of the ECM are required during the planar cell polarity (PCP) signalling-regulated cell movement of ommatidial rotation in the Drosophila eye. The loss-of-function mutations of integrins or ECM components cause defects in rotation, with mutant clusters rotating asynchronously compared to wild-type clusters. Initially, mutant clusters tend to rotate faster, and at later stages they fail to be synchronous with their neighbours, leading to aberrant rotation angles and resulting in a disorganized ommatidial arrangement in adult eyes. We further demonstrate that integrin localization changes dynamically during the rotation process. Our data suggest that core Frizzled/PCP factors, acting through RhoA and Rho kinase, regulate the function/activity of integrins and that integrins thus contribute to the complex interaction network of PCP signalling, cell adhesion and cytoskeletal elements required for a precise and synchronous 90° rotation movement.

scholarly journals Planar cell polarity controls directional Notch signaling in the Drosophila leg

Development ◽  
2012 ◽  
Vol 139 (14) ◽  
pp. 2584-2593 ◽  
Author(s):  
A. Capilla ◽  
R. Johnson ◽  
M. Daniels ◽  
M. Benavente ◽  
S. J. Bray ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity

scholarly journals The Drosophila melanogaster Suppressor of deltex Gene, a Regulator of the Notch Receptor Signaling Pathway, Is an E3 Class Ubiquitin Ligase

Genetics ◽  
1999 ◽  
Vol 152 (2) ◽  
pp. 567-576 ◽  
Author(s):  
M Cornell ◽  
D A P Evans ◽  
R Mann ◽  
M Fostier ◽  
M Flasza ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Ubiquitin Ligase ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Wing Vein ◽  
Cell Fate Decisions

Abstract During development, the Notch receptor regulates many cell fate decisions by a signaling pathway that has been conserved during evolution. One positive regulator of Notch is Deltex, a cytoplasmic, zinc finger domain protein, which binds to the intracellular domain of Notch. Phenotypes resulting from mutations in deltex resemble loss-of-function Notch phenotypes and are suppressed by the mutation Suppressor of deltex [Su(dx)]. Homozygous Su(dx) mutations result in wing-vein phenotypes and interact genetically with Notch pathway genes. We have previously defined Su(dx) genetically as a negative regulator of Notch signaling. Here we present the molecular identification of the Su(dx) gene product. Su(dx) belongs to a family of E3 ubiquitin ligase proteins containing membrane-targeting C2 domains and WW domains that mediate protein-protein interactions through recognition of proline-rich peptide sequences. We have identified a seven-codon deletion in a Su(dx) mutant allele and we show that expression of Su(dx) cDNA rescues Su(dx) mutant phenotypes. Overexpression of Su(dx) also results in ectopic vein differentiation, wing margin loss, and wing growth phenotypes and enhances the phenotypes of loss-of-function mutations in Notch, evidence that supports the conclusion that Su(dx) has a role in the downregulation of Notch signaling.

scholarly journals PLK-1 Regulation of Asymmetric Cell Division in the Early C. elegans Embryo

2021 ◽  
Vol 8 ◽  
Author(s):  
Amelia J. Kim ◽  
Erik E. Griffin
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Critical Role ◽  
Cell Cortex ◽  
C Elegans ◽  
Mitotic Kinase ◽  
Centrosome Separation

PLK1 is a conserved mitotic kinase that is essential for the entry into and progression through mitosis. In addition to its canonical mitotic functions, recent studies have characterized a critical role for PLK-1 in regulating the polarization and asymmetric division of the one-cell C. elegans embryo. Prior to cell division, PLK-1 regulates both the polarization of the PAR proteins at the cell cortex and the segregation of cell fate determinants in the cytoplasm. Following cell division, PLK-1 is preferentially inherited to one daughter cell where it acts to regulate the timing of centrosome separation and cell division. PLK1 also regulates cell polarity in asymmetrically dividing Drosophila neuroblasts and during mammalian planar cell polarity, suggesting it may act broadly to connect cell polarity and cell cycle mechanisms.

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