RT Journal Article
T1 An in vivo drug screen in zebrafish reveals that cyclooxygenase 2-derived prostaglandin D2 promotes spinal cord neurogenesis
A1 González Llera, Laura
A1 Sobrido Cameán, Daniel
A1 Quelle Regaldie, Ana
A1 Sánchez Piñón, Laura
A1 Barreiro Iglesias, Antón
K1 Prostaglandin D2
K1 Neurogenesis
K1 Central nervous system disorders
K1 Zebrafish
K1 Spinal cord
AB The study of neurogenesis is essential to understanding fundamental developmental processes and for the development of cell replacement therapies for central nervous system disorders. Here, we designed an in vivo drug screening protocol in developing zebrafish to find new molecules and signalling pathways regulating neurogenesis in the ventral spinal cord. This unbiased drug screen revealed that 4 cyclooxygenase (COX) inhibitors reduced the generation of serotonergic interneurons in the developing spinal cord. These results fitted very nicely with available single-cell RNAseq data revealing that floor plate cells show differential expression of 1 of the 2 COX2 zebrafish genes (ptgs2a). Indeed, several selective COX2 inhibitors and two different morpholinos against ptgs2a reduced the number of serotonergic neurons in the ventral spinal cord and led to locomotor deficits. Single-cell RNAseq data and different pharmacological manipulations further revealed that COX2-floor plate-derived prostaglandin D2 promotes neurogenesis in the developing spinal cord by promoting mitotic activity in progenitor cells. Rescue experiments using a phosphodiesterase-4 inhibitor suggest that intracellular changes in cAMP levels underlie the effects of COX inhibitors on neurogenesis and locomotion. Our study provides compelling in vivo evidence showing that prostaglandin signalling promotes neurogenesis in the ventral spinal cord.
PB Wiley
SN 0960-7722
YR 2023
FD 2023
LK http://hdl.handle.net/10347/32539
UL http://hdl.handle.net/10347/32539
LA eng
NO González-Llera, L., Sobrido-Cameán, D., Quelle-Regaldie, A., Sánchez, L., & Barreiro-Iglesias, A. (2023). An in vivo drug screen in zebrafish reveals that cyclooxygenase 2-derived prostaglandin D2 promotes spinal cord neurogenesis. Cell Proliferation, 1-14. https://doi.org/10.1111/cpr.13594
NO Grant PID2020-115121GB-I00 funded by MCIN/AEI/10.13039/501100011033 to A. Barreiro-Iglesias and L. Sánchez. Grant ED 431C 2021/18 funded by Xunta de Galicia. The European Molecular Biology Organization (EMBO) granted a long-term EMBO fellowship to D. Sobrido-Cameán (ALTF 62-2021).
DS Minerva
RD 1 may 2026