Eye suppression, a novel function of teashirt, requires Wingless signaling

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4271-4280 ◽  
Author(s):  
Amit Singh ◽  
Madhuri Kango-Singh ◽  
Y. Henry Sun

teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.

1992 ◽  
Vol 111 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Noriaki Shimizu ◽  
Mitsue ohta ◽  
Chie Fujiwara ◽  
Junji Sagara ◽  
Naoko Mochizuki ◽  
...  

2007 ◽  
Vol 109 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Christina Koesters ◽  
Bernd Unger ◽  
Ivan Bilic ◽  
Uwe Schmidt ◽  
Stefan Bluml ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1255-1255
Author(s):  
Giulia Morello ◽  
Sanja Aveic ◽  
Sonia Minuzzo ◽  
Barbara Michielotto ◽  
Silvia Bresolin ◽  
...  

Abstract Introduction MLL- rearranged acute myeloid leukemia (AML) remains a type of leukemia difficult to treat, for which alternative and more adequate treatment options are still urgently needed. The zinc finger protein 521 (ZNF521/EHZF) is a protein with multiple zinc finger domains that plays an essential role in the homeostasis of the hematopoietic stem/progenitor cell compartment. ZNF521 mRNA is highly expressed in hematopoietic stem and progenitor cells and its levels rapidly decrease during cell differentiation. Gene expression studies demonstrated that ZNF521 transcripts are abundantly expressed in MLL-rearranged AML. However, the functional significance of this up-regulation in AML with MLLrearrangements remains largely unknown. Methods and results Quantitative RT-PCR analysis (qRT-PCR) confirmed that ZNF521 expression was significantly up regulated in a cohort of MLL-rearranged pediatric AML patients (n=80) compared with other AML subtypes (n=30) together with healthy bone marrow samples (n=7, p<0.0001), and AML cell lines with MLL fusion (THP-1, NOMO-1, ML2). To investigate the role of ZNF521, we performed shRNA-mediated knockdown of ZNF521 in MLL-rearranged AML cell lines THP-1 and NOMO-1, in which a reduced transcript levels of 60-70% resulted in a severe reduction of proliferation and largely abolished colony formation in methylcellulose, where residual colonies were also smaller than control. Next, flow-cytometry analysis showed that observed proliferation reduction was associated with a block of cell cycle in G1 phase (shRNA/control vs shRNA/ZNF521 G1=45.4% vs G1=60.4%, n=3, p<0.05) and a late cell death induction (Annexin/PI positive cells: shRNA/control 21.4±0.5% vs shRNA/ZNF521 30.1±0.3% 3 weeks, n=3, p<0.0001). Subsequently, morphology analysis of May-Grunwald-Giemsa stained cytospins identified a large number of monocytic cells differentiating into macrophages. This observation was further validated by flow-cytometry analysis that confirmed the increased levels of CD11b and CD14 antigens as sign of monocytic differentiation, indicating a tendency of ZNF521 when over-expressed to prevent cell differentiation. Then, we treated THP-1 cells with ATRA to induce differentiation and demonstrated by qRT-PCR a significant reduction of ZNF521 mRNA expression, supporting its role in blocking differentiation in MLL-rearranged leukemic cells. Hence, to validate the specificity of these effects in vivo, we transplanted leukemic bone marrow cells from different MLL-AF9 AML pediatric patients (n=4) into immunodeficient mice. All mice developed AML by 7 to 9 weeks after transplantation. Then, the ex vivo cells were transduced with ZNF521 shRNA and showed morphology changes similar to those observed in vitro, with typical features of maturation. Conclusions Collectively, these results demonstrate that ZNF521 plays an important role in MLL-AF9-induced AML leukemia wherein it maintains a block of differentiation. Thus, our findings make ZNF521 a novel attractive target for therapeutic intervention in MLL-rearranged AML. However, further studies on the function of ZNF521 in MLL-rearranged AML and on the possibility to block it are required. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 383 (2) ◽  
pp. 111563 ◽  
Author(s):  
Sarah A. Lynch ◽  
Marc A. McLeod ◽  
Hannah C. Orsech ◽  
Alexander M. Cirelli ◽  
David S. Waddell

2008 ◽  
Vol 284 (6) ◽  
pp. 3480-3487 ◽  
Author(s):  
Etsuko Matsubara ◽  
Ikuya Sakai ◽  
Jun Yamanouchi ◽  
Hiroshi Fujiwara ◽  
Yoshihiro Yakushijin ◽  
...  

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