Optomotor-Blind Negatively Regulates Drosophila Eye Development by Blocking Jak/STAT Signaling

Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chien-Hung; Lin, Sheng-Wei; Sun, Yi; Pflugfelder, Gert O.

doi:10.1371/journal.pone.0120236

Cited by 7 publications

(7 citation statements)

References 89 publications

(112 reference statements)

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“…Proliferation of glia along the NER of A8/9 was assessed in third instar larvae using the phospho-histone H3 (pH3) antibody, which labels mitotic cells. Specificity of the pH3 antibody was confirmed by immunostaining third instar eye imaginal discs, which revealed a pattern of pH3 immunostaining consistent with previously published studies ( S1 Fig ) [ 42 ]. Along the A8/9 peripheral nerve, approximately 90% of glial cells were labeled with the pH3 antibody in the repo -Gal4 and repo -Gal4> dcr2 control samples ( Fig 4 ).…”

Section: Resultssupporting

confidence: 88%

Identification of raw as a regulator of glial development

2018

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Glial cells perform numerous functions to support neuron development and function, including axon wrapping, formation of the blood brain barrier, and enhancement of synaptic transmission. We have identified a novel gene, raw, which functions in glia of the central and peripheral nervous systems in Drosophila. Reducing Raw levels in glia results in morphological defects in the brain and ventral nerve cord, as well as defects in neuron function, as revealed by decreased locomotion in crawling assays. Examination of the number of glia along peripheral nerves reveals a reduction in glial number upon raw knockdown. The reduced number of glia along peripheral nerves occurs as a result of decreased glial proliferation. As Raw has been shown to negatively regulate Jun N-terminal kinase (JNK) signaling in other developmental contexts, we examined the expression of a JNK reporter and the downstream JNK target, matrix metalloproteinase 1 (mmp1), and found that raw knockdown results in increased reporter activity and Mmp1 levels. These results are consistent with previous studies showing increased Mmp levels lead to nerve cord defects similar to those observed upon raw knockdown. In addition, knockdown of puckered, a negative feedback regulator of JNK signaling, also causes a decrease in glial number. Thus, our studies have resulted in the identification of a new regulator of gliogenesis, and demonstrate that increased JNK signaling negatively impacts glial development.

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Section: Resultssupporting

confidence: 88%

Identification of raw as a regulator of glial development

2018

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“…Immunostaining of the eye discs carrying a STAT92E activity reporter, which contains 10 STAT92E binding sites linked to a GFP reporter gene (Bach et al, 2007), showed punctate GFP expression in the posterior part of the eye disc, which overlaps with the carpet glia (Figure 6C). We further examined the expression of a modified STAT92E activity reporter whose GFP is nucleus localized (Tsai et al, 2015) and found GFP expression in the carpet nuclei (Figure 6D). In addition, active JAK-STAT signaling was also found in the migratory RBGs and the PRs in the posterior part of the eye disc (Figure 6D).…”

Section: Resultsmentioning

confidence: 99%

“…The different UAS-dsRNA flies used in this study were obtained from the Vienna Drosophila Resource Center (VDRC) or the TRiP collection (BDSC): UAS-kay dsRNA (BDSC #27722, #31391), UAS-Rho1 dsRNA (BDSC #9909, #9910), and UAS-path dsRNA (VDRC #100519). Other fly lines used were UAS-Upd3 (Houtz et al, 2017; provided by Dr. Yu-Chen Tsai), 10xSTAT-GFP (Bach et al, 2007; provided by Dr. Y. Henry Sun), and 10xSTAT-GFP-nls (Tsai et al, 2015; provided by Dr. Yu-Chen Tsai).…”

Section: Methodsmentioning

confidence: 99%

Expressional Profiling of Carpet Glia in the Developing Drosophila Eye Reveals Its Molecular Signature of Morphology Regulators

Hung

et al. 2019

Front. Neurosci.

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Homeostasis in the nervous system requires intricate regulation and is largely accomplished by the blood–brain barrier (BBB). The major gate keeper of the vertebrate BBB is vascular endothelial cells, which form tight junctions (TJs). To gain insight into the development of the BBB, we studied the carpet glia, a subperineurial glial cell type with vertebrate TJ-equivalent septate junctions, in the developing Drosophila eye. The large and flat, sheet-like carpet glia, which extends along the developing eye following neuronal differentiation, serves as an easily accessible experimental system to understand the cell types that exhibit barrier function. We profiled transcribed genes in the carpet glia using targeted DNA adenine methyl-transferase identification, followed by next-generation sequencing (targeted DamID-seq) and found that the majority of genes expressed in the carpet glia function in cellular activities were related to its dynamic morphological changes in the developing eye. To unravel the morphology regulators, we silenced genes selected from the carpet glia transcriptome using RNA interference. The Rho1 gene encoding a GTPase was previously reported as a key regulator of the actin cytoskeleton. The expression of the pathetic ( path ) gene, encoding a solute carrier transporter in the developing eye, is specific to the carpet glia. The reduced expression of Rho1 severely disrupted the formation of intact carpet glia, and the silencing path impaired the connection between the two carpet glial cells, indicating the pan-cellular and local effects of Rho1 and Path on carpet glial cell morphology, respectively. Our study molecularly characterized a particular subperineurial cell type providing a resource for a further understanding of the cell types comprising the BBB.

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“…We also used the 10XSTAT-GFP reporter to determine whether the JAK-STAT pathway, which is activated by Upd1-3, is affected by dBRWD3 in PcG mutant cells [ 40 , 41 ]. In contrast to the weak and uniform expression observed in wild-type antennal discs ( Fig 3L and 3M , arrows), the GFP signal was much higher in Scm D1 mutant clones ( Fig 3N ), likely due to up-regulation of upd1-3 .…”

Section: Resultsmentioning

confidence: 99%

dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations

Shih¹,

Chen²,

Liu³

et al. 2016

PLoS Genet

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To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression) and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM)-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.

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Optomotor-Blind Negatively Regulates Drosophila Eye Development by Blocking Jak/STAT Signaling

Cited by 7 publications

References 89 publications

Identification of raw as a regulator of glial development

Identification of raw as a regulator of glial development

Expressional Profiling of Carpet Glia in the Developing Drosophila Eye Reveals Its Molecular Signature of Morphology Regulators

dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations

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