Control of photoreceptor cell morphology, planar polarity and epithelial integrity during Drosophila eye development

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2247-2258 ◽  
Author(s):  
Amanda T. Pickup ◽  
Michele L. Lamka ◽  
Qi Sun ◽  
Man Lun R. Yip ◽  
Howard D. Lipshitz
Keyword(s):  
Cell Fate ◽  
Cell Morphology ◽  
Photoreceptor Cell ◽  
Zinc Finger Protein ◽  
Photoreceptor Cells ◽  
Planar Polarity ◽  
Tracheal System ◽  
General Role ◽  
Epithelial Integrity ◽  
Jnk Signaling

We report that the hindsight (hnt) gene, which encodes a nuclear zinc-finger protein, regulates cell morphology, cell fate specification, planar cell polarity and epithelial integrity during Drosophila retinal development. In the third instar larval eye imaginal disc, HNT protein expression begins in the morphogenetic furrow and is refined to cells in the developing photoreceptor cell clusters just before their determination as neurons. In hnt mutant larval eye tissue, furrow markers persist abnormally posterior to the furrow, there is a delay in specification of preclusters as cells exit the furrow, there are morphological defects in the preclusters and recruitment of cells into specific R cell fates often does not occur. Additionally, genetically mosaic ommatidia with one or more hnt mutant outer photoreceptor cells, have planar polarity defects that include achirality, reversed chirality and misrotation. Mutants in the JNK pathway act as dominant suppressors of the hnt planar polarity phenotype, suggesting that HNT functions to downregulate JUN kinase (JNK) signaling during the establishment of ommatidial planar polarity. HNT expression continues in the photoreceptor cells of the pupal retina. When an ommatidium contains four or more hnt mutant photoreceptor cells, both genetically mutant and genetically wild-type photoreceptor cells fall out of the retinal epithelium, indicating a role for HNT in maintenance of epithelial integrity. In the late pupal stages, HNT regulates the morphogenesis of rhabdomeres within individual photoreceptor cells and the separation of the rhabdomeres of adjacent photoreceptor cells. Apical F-actin is depleted in hnt mutant photoreceptor cells before the observed defects in cellular morphogenesis and epithelial integrity. The analyses presented here, together with our previous studies in the embryonic amnioserosa and tracheal system, show that HNT has a general role in regulation of the F-actin-based cytoskeleton, JNK signaling, cell morphology and epithelial integrity during development.

Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3619-3629 ◽  
Author(s):  
U. Weber ◽  
N. Paricio ◽  
M. Mlodzik
Keyword(s):  
Cell Fate ◽  
Genetic Interaction ◽  
Function Analysis ◽  
Loss Of Function ◽  
Planar Polarity ◽  
Jnk Signaling ◽  
Drosophila Eye ◽  
Polarity Determination ◽  
Signaling Components

Jun acts as a signal-regulated transcription factor in many cellular decisions, ranging from stress response to proliferation control and cell fate induction. Genetic interaction studies have suggested that Jun and JNK signaling are involved in Frizzled (Fz)-mediated planar polarity generation in the Drosophila eye. However, simple loss-of-function analysis of JNK signaling components did not show comparable planar polarity defects. To address the role of Jun and JNK in Fz signaling, we have used a combination of loss- and gain-of-function studies. Like Fz, Jun affects the bias between the R3/R4 photoreceptor pair that is critical for ommatidial polarity establishment. Detailed analysis of jun(−) clones reveals defects in R3 induction and planar polarity determination, whereas gain of Jun function induces the R3 fate and associated polarity phenotypes. We find also that affecting the levels of JNK signaling by either reduction or overexpression leads to planar polarity defects. Similarly, hypomorphic allelic combinations and overexpression of the negative JNK regulator Puckered causes planar polarity eye phenotypes, establishing that JNK acts in planar polarity signaling. The observation that Dl transcription in the early R3/R4 precursor cells is deregulated by Jun or Hep/JNKK activation, reminiscent of the effects seen with Fz overexpression, suggests that Jun is one of the transcription factors that mediates the effects of fz in planar polarity generation.

Decoding vectorial information from a gradient: sequential roles of the receptors Frizzled and Notch in establishing planar polarity in the Drosophila eye

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5725-5738 ◽  
Author(s):  
A. Tomlinson ◽  
G. Struhl
Keyword(s):  
High Activity ◽  
Cell Fate ◽  
Photoreceptor Cells ◽  
The Other ◽  
Cell Fate Decision ◽  
Planar Polarity ◽  
Genetic Mosaics ◽  
Polar Cell ◽  
Drosophila Eye ◽  
Fate Decision

The Drosophila eye is composed of several hundred ommatidia that can exist in either of two chiral forms, depending on position: ommatidia in the dorsal half of the eye adopt one chiral form, whereas ommatidia in the ventral half adopt the other. Chirality appears to be specified by a polarizing signal with a high activity at the interface between the two halves (the ‘equator’), which declines in opposite directions towards the dorsal and ventral poles. Here, using genetic mosaics, we show that this polarizing signal is decoded by the sequential use of two receptor systems. The first depends on the seven-transmembrane receptor Frizzled (Fz) and distinguishes between the two members of the R3/R4 pair of presumptive photoreceptor cells, predisposing the cell that is located closer to the equator and having higher Fz activity towards the R3 photoreceptor fate and the cell further away towards the R4 fate. This bias is then amplified by subsequent interactions between the two cells mediated by the receptor Notch (N) and its ligand Delta (Dl), ensuring that the equatorial cell becomes the R3 photoreceptor while the polar cell becomes the R4 photoreceptor. As a consequence of this reciprocal cell fate decision, the R4 cell moves asymmetrically relative to the R3 cell, initiating the appropriate chiral pattern of the remaining cells of the ommatidium.

scholarly journals Specification of cell fate in the developing eye of Drosophila

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 123-130 ◽  
Author(s):  
Ernst Hafen ◽  
Konrad Basler
Keyword(s):  
Tyrosine Kinase ◽  
Cell Fate ◽  
Photoreceptor Cell ◽  
Nuclear Protein ◽  
Single Cells ◽  
Photoreceptor Cells ◽  
Positional Information ◽  
Cellular Interactions ◽  
Eye Imaginal Disc

Determination of cell fate in the developing eye of Drosophila depends on cellular interactions. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, single cells are specified in regular intervals to become the R8 photoreceptor cells. Genes such as Notch and scabrous participate in this process suggesting that specification of ommatidial founder cells and the formation of bristles in the adult epidermis involve a similar mechanism known as lateral inhibition. The subsequent steps of ommatidial assembly involve a different mechanism: undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell is best understood. The key role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information – most likely encoded by boss on the neighboring R8 cell membrane – into the cell via its tyrosine kinase that activates a signal transduction cascade. Two components of this cascade – Sos and sina – have been identified genetically, sina encodes a nuclear protein whose expression is not limited to R7. Constitutive activation of the sevenless kinase by overexpression results in the diversion of other ommatidial cells into the R7 pathway, suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development.

ming is expressed in neuroblast sublineages and regulates gene expression in the Drosophila central nervous system

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 943-952 ◽  
Author(s):  
X. Cui ◽  
C.Q. Doe
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Fate ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cell Lineage ◽  
Cell Lineages ◽  
Finger Protein ◽  
Cell Diversity

Cell diversity in the Drosophila central nervous system (CNS) is primarily generated by the invariant lineage of neural precursors called neuroblasts. We used an enhancer trap screen to identify the ming gene, which is transiently expressed in a subset of neuroblasts at reproducible points in their cell lineage (i.e. in neuroblast ‘sublineages’), suggesting that neuroblast identity can be altered during its cell lineage. ming encodes a predicted zinc finger protein and loss of ming function results in precise alterations in CNS gene expression, defects in axonogenesis and embryonic lethality. We propose that ming controls cell fate within neuroblast cell lineages.

Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 815-824 ◽  
Author(s):  
M.B. Rogers ◽  
B.A. Hosler ◽  
L.J. Gudas
Keyword(s):  
Retinoic Acid ◽  
Germ Cell ◽  
Cell Fate ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Preimplantation Embryos ◽  
Specific Expression

We have previously isolated a cDNA clone for a gene whose expression is reduced by retinoic acid (RA) treatment of F9 embryonal carcinoma cells. The nucleotide sequence indicated that this gene, Rex-1, encodes a zinc-finger protein and thus may be a transcriptional regulator. The Rex-1 message level is high in two lines of embryonic stem cells (CCE and D3) and is reduced when D3 cells are induced to differentiate using four different growth conditions. As expected for a stem-cell-specific message, Rex-1 mRNA is present in the inner cell mass (ICM) of the day 4.5 mouse blastocyst. It is also present in the polar trophoblast of the blastocyst. One and two days later, Rex-1 message is found in the ectoplacental cone and extraembryonic ectoderm of the egg cylinder (trophoblast-derived tissues), but its abundance is much reduced in the embryonic ectoderm which is directly descended from the ICM. Rex-1 is expressed in the day 18 placenta (murine gestation is 18 days), a tissue which is largely derived from trophoblast. The only tested adult tissue that contains detectable amounts of Rex-1 mRNA is the testis. In situ hybridization and northern analyses of RNA from germ-cell-deficient mouse testis and stage-specific germ cell preparations suggest that Rex-1 expression is limited to spermatocytes (germ cells undergoing meiosis). These results suggest that Rex-1 is involved in trophoblast development and spermatogenesis, and is a useful marker for studies of early cell fate determination in the ICM.

scholarly journals Activation of JNK signaling promotes all-trans-retinal–induced photoreceptor apoptosis in mice

2020 ◽  
Vol 295 (20) ◽  
pp. 6958-6971
Author(s):  
Chunyan Liao ◽  
Binxiang Cai ◽  
Yufeng Feng ◽  
Jingmeng Chen ◽  
Yiping Wu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Intraperitoneal Administration ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Jnk Signaling ◽  
Age Related ◽  
Dry Amd ◽  
Induced Apoptosis ◽  
Jnk Activation ◽  
Species Production

Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4−/−Rdh8−/− mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4−/−Rdh8−/− mice. Of note, intraperitoneal administration of JNK–IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4−/−Rdh8−/− mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.

scholarly journals Restriction of memory B cell differentiation at the germinal center B cell positive selection stage

2020 ◽  
Vol 217 (7) ◽  
Author(s):  
Amparo Toboso-Navasa ◽  
Arief Gunawan ◽  
Giulia Morlino ◽  
Rinako Nakagawa ◽  
Andrea Taddei ◽  
...  
Keyword(s):  
B Cells ◽  
Positive Selection ◽  
B Cell ◽  
Cell Fate ◽  
Germinal Center ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
B Cell Differentiation ◽  
Repressor Complex ◽  
Selection Stage

Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs. MYC is transiently induced in cells fated for GC expansion and plasma cell (PC) formation, so-called positively selected GC B cells. We found that these cells coexpressed MYC and MIZ1 (MYC-interacting zinc-finger protein 1 [ZBTB17]). MYC and MIZ1 are transcriptional activators; however, they form a transcriptional repressor complex that represses MIZ1 target genes. Mice lacking MYC–MIZ1 complexes displayed impaired cell cycle entry of positively selected GC B cells and reduced GC B cell expansion and PC formation. Notably, absence of MYC–MIZ1 complexes in positively selected GC B cells led to a gene expression profile alike that of MBCs and increased MBC differentiation. Thus, at the GC positive selection stage, MYC–MIZ1 complexes are required for effective GC expansion and PC formation and to restrict MBC differentiation. We propose that MYC and MIZ1 form a module that regulates GC B cell fate.

scholarly journals Receptor-mediated activation of recombinant Trpl expressed in Sf9 insect cells

1995 ◽  
Vol 305 (2) ◽  
pp. 605-611 ◽  
Author(s):  
Y Hu ◽  
W P Schilling
Keyword(s):  
Photoreceptor Cell ◽  
Receptor Potential ◽  
Photoreceptor Cells ◽  
Sharp Contrast ◽  
Membrane Receptors ◽  
Cation Channels ◽  
Sf9 Cells ◽  
Baculovirus Expression ◽  
Baculovirus Expression Vector ◽  
Stimulation Of

The Drosophila proteins, Trp and Trpl, are suggested to be cation channels responsible for depolarization of the receptor potential associated with stimulation of insect photoreceptor cells by light. Consistent with this hypothesis, we recently showed that recombinant Trpl forms Ca(2+)- and Ba(2+)-permeable non-selective cation channels when expressed in Sf9 cells using the baculovirus expression vector. As Trpl may be activated in the photoreceptor cell after stimulation of phospholipase C, we hypothesized that a similar regulation of recombinant Trpl may be observed in the Sf9 cell after activation of heterologous membrane receptors linked to Ca(2+)-signal-transduction pathways. To test this hypothesis, Ca2+ signalling was examined in Fura-2-loaded Sf9 cells infected with baculovirus containing cDNA for the M5 muscarinic receptor alone (M5 cells) or in cells co-infected with both M5 and Trpl-containing baculoviruses (M5-Trpl cells). Addition of carbachol (100 microM) to M5 cells produced an increase in cytosolic free Ca2+ concentration ([Ca2+]i) (mean +/- S.D.; n = 17) from 101 +/- 20 to 762 +/- 178 nM which declined to a sustained elevated level of 384 +/- 102 nM after 3 min. The sustained component was eliminated by removal of extracellular Ca2+ or by addition of La3+ or Gd3+ (10 microM). In M5-Trpl cells, basal [Ca2+]i increased as a function of time after infection. To evaluate the contribution of Ca2+ influx to the overall profile observed, Ba2+, a Ca2+ surrogate that is not a substrate for the Ca2+ pump, was used. The increase in basal [Ca2+]i seen in M5-Trpl cells was associated with an increase in basal Ba2+ influx. Addition of carbachol to M5-Trpl cells at 30-36 h after infection produced a large increase in [Ca2+]i to a sustained value of 677 +/- 143 nM. This change in [Ca2+]i was (1) blocked by atropine, (2) attenuated in the absence of extracellular Ca2+, and (3) relatively insensitive to La3+, but blocked by Gd3+ in the 0.1-1 mM range. In the presence of 10 microM Gd3+ to block the endogenous-receptor-mediated Ca(2+)-influx in M5-Trpl cells. In sharp contrast increase in Ba2+ influx in M5-Trpl cells. In sharp contrast, neither Ca2+ nor Ba2+ influx through Trpl was affected by thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca(2+)-ATPase pump.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Phagocytosis of Retinal Rod and Cone Photoreceptors

Physiology ◽  
2010 ◽  
Vol 25 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Brian M. Kevany ◽  
Krzysztof Palczewski
Keyword(s):  
Outer Segment ◽  
Photoreceptor Cell ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Constant Length ◽  
Outer Segments ◽  
Retinal Rod ◽  
Rod And Cone Photoreceptors

Photoreceptor cells maintain a roughly constant length by continuously generating new outer segments from their base while simultaneously releasing mature outer segments engulfed by the retinal pigment epithelium (RPE). Thus postmitotic RPE cells phagocytose an immense amount of material over a lifetime, disposing of photoreceptor cell waste while retaining useful content. This review focuses on current knowledge of outer segment phagocytosis, discussing the steps involved along with their critical participants as well as how various perturbations in outer segment (OS) disposal can lead to retinopathies.

scholarly journals Molecular Characterization of abLIM, a Novel Actin-binding and Double Zinc Finger Protein

1997 ◽  
Vol 138 (3) ◽  
pp. 575-588 ◽  
Author(s):  
Dorothy J. Roof ◽  
Annmarie Hayes ◽  
Michael Adamian ◽  
Athar H. Chishti ◽  
Tiansen Li
Keyword(s):  
Zinc Finger ◽  
Intracellular Signaling ◽  
Time Course ◽  
Zinc Finger Protein ◽  
Binding Capacity ◽  
Consensus Sequence ◽  
Developmental Expression ◽  
Actin Binding ◽  
General Role ◽  
Outer Segments

Molecules that couple the actin-based cytoskeleton to intracellular signaling pathways are central to the processes of cellular morphogenesis and differentiation. We have characterized a novel protein, the actin-binding LIM (abLIM) protein, which could mediate such interactions between actin filaments and cytoplasmic targets. abLIM protein consists of a COOH-terminal cytoskeletal domain that is fused to an NH2-terminal domain consisting of four double zinc finger motifs. The cytoskeletal domain is ∼50% identical to erythrocyte dematin, an actin-bundling protein of the red cell membrane skeleton, while the zinc finger domains conform to the LIM motif consensus sequence. In vitro expression studies demonstrate that abLIM protein can bind to F-actin through the dematin-like domain. Transcripts corresponding to three distinct isoforms have a widespread tissue distribution. However, a polypeptide corresponding to the full-length isoform is found exclusively in the retina and is enriched in biochemical extracts of retinal rod inner segments. abLIM protein also undergoes extensive phosphorylation in light-adapted retinas in vivo, and its developmental expression in the retina coincides with the elaboration of photoreceptor inner and outer segments. Based on the composite primary structure of abLIM protein, actin-binding capacity, potential regulation via phosphorylation, and isoform expression pattern, we speculate that abLIM may play a general role in bridging the actin-based cytoskeleton with an array of potential LIM protein-binding partners. The developmental time course of abLIM expression in the retina suggests that the retina-specific isoform may have a specialized role in the development or elaboration of photoreceptor inner and outer segments.

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