IRE1 Activation in Spinal Cord Development and Repair in the Zebrafish Model
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Date
2024-07-05
Authors
Talabis, Kayla
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Abstract
The Unfolded Protein Response (UPR) is a cellular pathway that functions in the maintenance of proteostasis in response to endoplasmic reticulum (ER) stress. Recent studies implicate the IRE1 branch of the UPR in the development of the central nervous system (CNS) and in response to spinal cord injury (SCI). To date, studies have focused mainly on mammalian models and thus we know little about the role of the UPR in the CNS of other vertebrates. In this study, we take advantage of the many attributes of the zebrafish model, including its capacity for neurorepair, to investigate the activation of IRE1 during spinal cord development and following SCI. Using the Tg(xbp1s:eGFP) transgenic reporter fish that expresses GFP upon IRE1 activation, we show that IRE1 is strongly upregulated in early larvae compared to juveniles and adults. High levels of IRE1 expression are displayed at 4-days post fertilization (dpf) and drop off into adulthood. Interestingly, when exposed to the ER stress inducing drug Dithiothreitol (DTT), larvae at 4-dpf also show slight elevated levels of IRE1 activation compared to later stages of development, suggesting IRE1 is less inducible with age. We next established a larval SCI model to ask whether IRE1 expression was upregulated after SCI. We demonstrate that, in contrast to mammalian models, spinal cord IRE1 activity remains the same or slightly decreases following SCI.
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Keywords
Unfolded Protein Response, zebrafish model, spinal cord injury