scholarly journals The sex determination master switch, Sex-lethal, responds to Hedgehog signaling in theDrosophilagermline

Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2649-2660 ◽  
Author(s):  
Cynthia Vied ◽  
Jamila I. Horabin

Sex-lethal is the Drosophila melanogaster sex determination master switch. It is also required in female germ cells to control mitosis and meiotic recombination. As early germ cells mature, distinct changes in both Sex-lethal protein levels and localization occur. By manipulating the levels of Hedgehog and making germline clones of components in the hedgehog signaling pathway, we demonstrate that Hedgehog affects the nuclear translocation of Sex-lethal and the levels of the protein in early germ cells. This effect is mediated primarily through degradation. Consistent with the Hedgehog pathway regulating Sex-lethal, we find Sex-lethal in a complex with Fused and Costal-2, both downstream components of the pathway. This is the first demonstration that downstream components of the Hedgehog signaling pathway regulate a target other than Cubitus interruptus.

Author(s):  
Yuan Gu ◽  
Xiaochen Liu ◽  
Lele Liao ◽  
Yongquan Gao ◽  
Yu Shi ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.


Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2894-2903 ◽  
Author(s):  
Shinichi Miyagawa ◽  
Daisuke Matsumaru ◽  
Aki Murashima ◽  
Akiko Omori ◽  
Yoshihiko Satoh ◽  
...  

During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.


2004 ◽  
Vol 323 (2) ◽  
pp. 523-533 ◽  
Author(s):  
Norihisa Shindo ◽  
Atsushi Sakai ◽  
Kouji Yamada ◽  
Toru Higashinakagawa

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