Semaphorin/plexin interactions in regenerative neurogenesis in zebrafish
Biotechnology and Biological Sciences Research Council
Technical University Dresden
Zebrafish, in contrast to mammals, show regeneration of neurons after spinal cord injury. The immune reaction to injury promotes regenerative neurogenesis in zebrafish, but how cross-talk between immune cells and neural progenitors occurs is poorly understood. We hypothesize that immune cells signal directly to neural progenitor cells via semaphorins to promote neurogenesis. In pilot studies using single cell RNAseq we determined that reactive macrophages show a 6-fold increase in sema4ab expression and that spinal progenitor cells express the receptors plexinb1a and plexinb1b after injury. We will determine spatiotemporal expression patterns of sema4ab and its ligands, and determine their functional roles by assessing progenitor cell proliferation and neuronal differentiation in mutants for ligand and receptors. To establish whether direct signalling occurs, we will expose neural progenitors to recombinant Sema4ab ex vivo and quantify regulation of neurogenesis-associated genes. To distinguish between effects in immune cell and neural progenitors, we will conditionally ablate plexinb1 function only in neural progenitor cells in vivo and determine regenerative outcome. This project will elucidate at the fundamental level if and how immune cells directly influence spinal progenitor cells after injury. This will provide targets for future interventions in non-regenerating mammals.
1.1 Normal biological development and functioning / Responsive Mode