Cellular automata modeling suggests symmetric stem-cell division, cell death, and cell drift as key mechanisms driving adult spinal cord growth in teleost fish

Abstract

Adult neurogenesis – the generation of neurons during adulthood – is intensively studied, yet little is known about its consequences at the tissue level. In the teleost fish Apteronotus leptorhynchus, morphometric analysis has revealed that the total number of cells in the spinal cord increases continuously throughout adulthood, driven by the activity of neurogenic stem/progenitor cells in both the ependymal layer at the central canal and in the radially located parenchyma. This net increase in cell numbers demonstrates cellular addition, as opposed to cellular turnover which appears to be the common outcome of adult neurogenesis in mammals. Grounded on a comprehensive set of quantitative data generated through high-resolution mapping of stem cells and their progeny, we constructed a cellular automata model of the stem-cell-driven growth of the spinal cord. Simulations based on this model suggest that three cellular mechanisms play a critical role for promoting sustained tissue growth and acquisition of correct form of the spinal cord, including the development of the ependymal layer and the parenchyma: the number of symmetric stem-cell divisions versus asymmetric divisions; the probability of the progeny of progenitor cells to undergo cell death; and the radial drifting of cells.