Biology subjects

Roehl, H.

Publications and source records attributed to Roehl, H..

4 recordsLinked to original sources

bioRxiv2021

Tetraspanin Cd9b plays a role in fertility in zebrafish

In mice, CD9 expression on the egg is required for efficient sperm-egg fusion and no effects on ovulation or male fertility are observed in CD9 null animals. Here we show that cd9b KO zebrafish also appear to have fertility defects. In contrast to mice, fewer eggs were laid by cd9b KO zebrafish pairs and, of the eggs laid, a lower percentage were fertilised. In vitro fertilization (IVF) was used to demonstrate that factors such as courting behaviour, adult size and mate choice were not causing the unexpected decrease in clutch size. The decrease in egg numbers could be rescued by exchanging either cd9b KO partner, male or female, for a wildtype (WT) partner. However, the fertilisation defect could only be rescued by crossing a cd9b KO female with a WT male. Our results indicate that Cd9b has several roles in fish fertility, affecting both clutch size and egg fertilisation. HighlightsO_LIcd9b mutant pairs lay fewer eggs and of the eggs laid, fewer are fertilised. C_LIO_LIMutation in cd9b does not affect primordial germ cell number or migration. C_LIO_LIReduction in number of eggs and fertility is not due to courting behaviour, fish size or mate choice. C_LIO_LIcd9b mutation in either gender affects the number of eggs laid. C_LIO_LIMutation of cd9b in the males affects fertilisation efficiency but mutation of cd9b in the females does not. C_LI

developmental biology↗

bioRxiv2021

CD9 tetraspanins convey robustness to CXCR4b signalling during collective cell migration

Collective cell migration is essential for embryonic development and homeostatic processes. During zebrafish development, the posterior lateral line primordium (pLLP) navigates along the embryo flank by collective cell migration. The chemokine receptors, Cxcr4b and Cxcr7b, as well as their cognate ligand, Cxcl12a, are essential for this process. We corroborate that knockdown of the zebrafish cd9 tetraspanin orthologue, cd9b, results in mild pLL abnormalities. Through generation of CRISPR and TALEN mutants, we show that cd9a and cd9b function partially redundantly in pLLP migration, which is delayed in the cd9b single and cd9a; cd9b double mutants. This delay led to a transient reduction in neuromast numbers. Loss of both Cd9a and Cd9b sensitized embryos to reduced Cxcr4b and Cxcl12a levels. Together these results provide evidence that Cd9 modulates collective cell migration of the pLLP during zebrafish development. One interpretation of these observations is that Cd9 contributes to more effective chemokine signalling.

developmental biology↗

bioRxiv2020

Irradiated mesenchymal stromal cells induce genetic instability in human CD34+ cells

Radiation-induced bystander effects (RIBE) in human hematopoietic stem and progenitor cells may initiate myeloid neoplasms (MN). Here, the occurrence of RIBE caused by genotoxic signaling from irradiated human mesenchymal stromal cells (MSC) on human bone marrow CD34+ cells was investigated. For this purpose, healthy MSC were irradiated in order to generate conditioned medium containing potential genotoxic signaling factors. Afterwards, healthy CD34+ cells from the same donors were grown in conditioned medium and RIBE were analyzed. Increased DNA damage and chromosomal instability were detected in CD34+ cells grown in MSC conditioned medium when compared to CD34+ cells grown in control medium. Furthermore, reactive oxygen species and distinct proteome alterations, e.g., heat-shock protein GRP78, that might be secreted into the extracellular medium, were identified as potential RIBE mediators. In summary, our data provide evidence that irradiated MSC induce genetic instability in human CD34+ cells potentially resulting in the initiation of MN. Furthermore, the identification of key bystander signals, such as GRP78, may lay the framework for the development of next-generation anti-leukemic drugs.

cancer biology↗

bioRxiv2018

Damage-induced reactive oxygen species enable regenerative signalling by the rapid repositioning of Hedgehog expressing cells.

Aquatic vertebrates have a remarkable ability to regenerate limbs and tails after amputation. Previous studies indicate that reactive oxygen species (ROS) signaling initiates regeneration, but the mechanism by which this takes place is poorly understood. Developmental signalling pathways have been shown to have pro-regenerative roles in many systems. However, whether these are playing roles that are specific to regeneration, or are simply recapitulating their developmental functions is unclear. We have analysed zebrafish larval tail regeneration and find evidence that ROS released upon wounding cause repositioning of notochord cells to the damage site. These cells secrete Hedgehog ligands which are required for regeneration. Hedgehog signalling is not required for normal tail development suggesting that it has a regeneration specific role. Our results provide a model for how ROS initiate tail regeneration, and indicate that developmental signaling pathways can play regenerative functions that are not directly related to their developmental roles.

developmental biology↗