Role of the hypoxia response pathway in lens formation during embryonic development of Xenopus laevis

Abstract

The RING finger ubiquitin ligase seven in absentia homolog 2 (Siah2) was identified in the R7 photoreceptor cells of Drosophila melanogaster, and it regulates the stability of prolyl hydroxylase domains (PHDs), with a concomitant effect on HIF-1α availability in the hypoxia response pathway. We previously reported that the hypoxia response pathway contributes to eye development during the embryonic development of Xenopus laevis. In this paper, the role of Siah2-mediated hypoxia response pathway in eye development of X. laevis embryos was further characterized. Xenopus Siah2 (xSiah2) mRNA was detected in lens tissue and xSiah2 overexpression caused a thickened lens placode, leading to loss of the optic lens. In embryos overexpressing xSiah2, lens marker gene transcription was reduced, suggesting that xSiah2 contributes to lens formation. xSiah2 overexpression decreased Xenopus PHD accumulation and increased Xenopus HIF-1α (xHIF-1α) accumulation. xHIF-1α degeneration with resveratrol restored the optical abnormality caused by xSiah2 overexpression, suggesting that the xSiah2-mediated hypoxia response pathway contributes to lens formation. Moreover, xSiah2 overexpression decreased endothelial–mesenchymal transition (EMT)-related Notch signaling-responsive genes transcription during the invasion of the lens placode. Our results suggest that the hypoxia response pathway plays an important role in the regulation of the EMT via the Notch signaling pathway during lens formation.

A comprehensive spatial-temporal transcriptomic analysis of differentiating nascent mouse lens epithelial and fiber cells

“…Many canonical signaling pathways in lens development are enriched in both epithelium and fiber higher expressed genes, including “ERK/MAPK Signaling” (Lovicu and McAvoy, 2001), “BMP signaling pathway”, “TGF-β signaling”, and “HIPPO signaling” (Cvekl and Zhang, 2017). In addition to these four pathways that are well established in lens development, the “NRF2-mediated oxidative stress response” term implicates redox-regulation in lens development, consistent with the formation of hypoxic conditions during lens embryogenesis (Baba et al, 2013).…”

Antioxidant and Protective Mechanisms against Hypoxia and Hypoglycaemia in Cortical Neurons in Vitro

“…HIFs are ubiquitously expressed in several mammalian cell types [ 29 ]. Since its discovery, the HIFs cascade has been extensively studied and plays a role in both physiological, as tissue repair, and pathological process [ 30 – 32 ], as ischemia [ 33 , 34 ].…”