Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development

Nguyen, Duy; Fayol, Olivier; Buisine, Nicolas; Lecorre, Pierrette; Uguen, Patricia

doi:10.1371/journal.pone.0155438

Cited by 6 publications

(6 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Figsupporting

confidence: 89%

“…2J (n > 10 for each) (I). The en>GFP, p35 wings were small and defective, similar to previous reports that overexpression of p35 causes developmental defects in eyes and wings (Katanayeva et al, 2010;Nguyen et al, 2016). Ubq-ana3-GFP, CS, and ana3 SH0558 /CyO-GFP larvae were irradiated with 1,000, 1,250, and 1,500 rad during 2nd to 3rd instar larval stages, and the number of adults was divided by the number of total empty pupal cases to obtain survival rates.…”

Section: Overexpression Of Ana3 Increases Cell Survivalsupporting

confidence: 74%

See 1 more Smart Citation

Anastral Spindle 3/Rotatin Stabilizes Sol narae and Promotes Cell Survival in Drosophila melanogaster

Cho

Lee

Cho

2021

Molecules and Cells

View full text Add to dashboard Cite

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that ana3m19 is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. ana3m19 has a nonsense mutation that truncates the highly conserved carboxyl terminal region containing multiple Armadillo repeats. Lethality induced by Sona overexpression was completely rescued by knockdown of Ana3, and the small and malformed wing and hinge phenotype induced by the knockdown of Ana3 was also normalized by Sona overexpression, establishing a mutually positive genetic interaction between ana3 and sona. p35 inhibited apoptosis and rescued the small wing and hinge phenotype induced by knockdown of ana3 . Furthermore, overexpression of Ana3 increased the survival rate of irradiated flies and reduced the number of dying cells, demonstrating that Ana3 actively promotes cell survival. Knockdown of Ana3 decreased the levels of both intra- and extracellular Sona in wing discs, while overexpression of Ana3 in S2 cells dramatically increased the levels of both cytoplasmic and exosomal Sona due to the stabilization of Sona in the lysosomal degradation pathway. We propose that one of the main functions of Ana3 is to stabilize Sona for cell survival and proliferation.

show abstract

Section: Figsupporting

confidence: 89%

Section: Overexpression Of Ana3 Increases Cell Survivalsupporting

confidence: 74%

Anastral Spindle 3/Rotatin Stabilizes Sol narae and Promotes Cell Survival in Drosophila melanogaster

Cho

Lee

Cho

2021

Molecules and Cells

View full text Add to dashboard Cite

show abstract

“…These results suggested that the transcription pausing function of M1BP may have similar target in the eye and wing imaginal disc. Recently, HEXIM, another transcriptional regulator associated with pol II pausing, has been reported to affect wing development in Drosophila by regulating Hh signaling 97 . In Drosophila wing imaginal disc, HEXIM knockdown causes developmental defects by inducing ectopic expression of hh and its transcriptional effector cubitus interuptus (ci), which triggers apoptosis.…”

Section: M1bp Blocks Wg Upregulation Mediated Developmental Cell Deatmentioning

confidence: 99%

Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila

Raj

Chimata

Singh

2020

Sci Rep

View full text Add to dashboard Cite

The phenomenon of RNA polymerase II (Pol II) pausing at transcription start site (TSS) is one of the key rate-limiting steps in regulating genome-wide gene expression. In Drosophila embryo, Pol II pausing is known to regulate the developmental control genes expression, however, the functional implication of Pol II pausing during later developmental time windows remains largely unknown. A highly conserved zinc finger transcription factor, Motif 1 Binding Protein (M1BP), is known to orchestrate promoter-proximal pausing. We found a new role of M1BP in regulating Drosophila eye development. Downregulation of M1BP function suppresses eye fate resulting in a reduced eye or a “no-eye” phenotype. The eye suppression function of M1BP has no domain constraint in the developing eye. Downregulation of M1BP results in more than two-fold induction of wingless (wg) gene expression along with robust induction of Homothorax (Hth), a negative regulator of eye fate. The loss-of-eye phenotype of M1BP downregulation is dependent on Wg upregulation as downregulation of both M1BP and wg, by using wgRNAi, shows a significant rescue of a reduced eye or a “no-eye” phenotype, which is accompanied by normalizing of wg and hth expression levels in the eye imaginal disc. Ectopic induction of Wg is known to trigger developmental cell death. We found that upregulation of wg as a result of downregulation of M1BP also induces apoptotic cell death, which can be significantly restored by blocking caspase-mediated cell death. Our data strongly imply that transcriptional regulation of wg by Pol II pausing factor M1BP may be one of the important regulatory mechanism(s) during Drosophila eye development.

show abstract

“…We addressed this point in our more recent paper [7]. We showed that organ failures to develop in HEXIM knockdown mutants was not a trivial consequence of the death of precursor cells.…”

Section: Physiological and Developmental Importance Of Heximmentioning

confidence: 99%