Biology subjects

Quelle-Regaldie, A.

Publications and source records attributed to Quelle-Regaldie, A..

2 recordsLinked to original sources

bioRxiv2023

An in vivo drug screen reveals that cyclooxygenase 2-derived prostaglandin D2 promotes spinal cord neurogenesis.

The study of neurogenesis is essential to understand 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 reduce the generation of serotonergic interneurons in the developing spinal cord. These results fitted very nicely with available single cell RNAseq data revealing that the floor plate cells show differential expression of 1 of the 2 COX2 zebrafish genes (ptgs2a). Indeed, several selective COX2 inhibitors and 2 different morpholinos against ptgs2a also caused a significant reduction in 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.

developmental biology↗

bioRxiv2021

Decline in constitutive proliferative activity in the zebrafish retina with ageing

It is largely assumed that the teleost retina shows continuous and active proliferative and neurogenic activity throughout life. But when deepening in the teleost literature one finds that assumptions about a highly active and continuous proliferation in the adult retina are based on studies in which proliferation was not quantified in a comparative way at the different life stages or was mainly studied in juveniles/young adults. Here, we performed a systematic and comparative study of the constitutive proliferative activity of the retina from early developing (2 days post-fertilization) to aged (up to 3-4 years post-fertilization) zebrafish. Mitotic activity and cell cycle progression were analyzed by using immunofluorescence against pH3 and PCNA, respectively. We observed a decline in cell proliferation in the retina with ageing, even despite the occurrence of a wave of secondary proliferation during sexual maturation. During this wave of secondary proliferation the distribution of proliferating and mitotic cells changes from the inner to the outer nuclear layer in the central retina. Importantly, in aged zebrafish there is a virtual disappearance of mitotic activity. Our results showing a decline in proliferative activity of the zebrafish retina with ageing are of crucial importance since it is generally assumed that the fish retina has continuous proliferative activity throughout life.

neuroscience↗