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Authors & Affiliations
Rita Varga, Angelika Varga, Kirsten Roberts, Peter Szucs, Zoltan Meszar
Abstract
After neurulation, neuroprogenitor cells differentiate into postmitotic neurons that migrate away from the ventricular zone and form a laminated structure in the spinal cord. Semaphorins are crucial for neuronal differentiation, particularly in axon pathfinding. Although semaphorin receptors are expressed in the ventricular zone of the developing spinal cord, their role in the neuronal cell cycle is not yet clear. Our study suggests that Sema 3 and their neuropilin receptors may be involved in a process that we disrupted using in-ovo electroporation. We overexpressed dominant-negative forms of the neuropilin receptors in the chicken spinal cord and analyzed the samples using histology, RNAseq, and simple western assay. In both cases, we found obvious anatomical spinal cord abnormalities involving syringomyelia. Compared to the GFP-expressing control, we found that cells expressing either the dominant-negative neuropilin 1 or 2 remained in the ventricular zone even after three days of survival, and these cells became apoptotic. However, these treated spinal cord progenitors seemed to be arrested in the cell cycle and showed a marked increase in the expression of PCNA, vimentin, and other cell cycle markers. RNAseq analysis indicates that both Npn1 and Npn2 play a crucial role in intracellular transport, transcription, and translation. Disruption of signalization via both receptors led to increased transcription but decreased translation. The results of this study provide valuable insights into the role of secreted semaphorins and their receptors in the early phase of neuronal differentiation.