The lab of Dr. Seth Blackshaw Professor of Neuroscience in the Solomon H. Snyder Department of Neuroscience published a paper in Science that maps out the network of genes that controls the ability of retinal neurons to regenerate from glial support cells. The paper’s lead authors, Thanh Hoang and Jie Wang, comprehensively analyzed changes in gene action that occur in retinal glial cells following injury three species – zebrafish, chickens and mice – which differ in their ability to generate retinal neurons in response to injury. Zebrafish can robustly regenerate neurons, newly hatched chicks can do so weakly and mice, like humans, cannot do so at all. This study found that retinal glial cells from all three species transition to an activated stage following injury, and that this is required for glia to be able to generate neurons in zebrafish and chicks, but identified a gene regulatory network in mice that actively blocked this process. By inactivating NFI family transcription factors, which are part of this network, Blackshaw’s group was able to induce mouse glia to generate retinal neurons. This demonstrates that mammals possess a latent ability to regenerate neurons lost to injury and disease, and that this can be awakened by disrupting genes in this network. This approach may be useful in cell-based therapies aimed at restoring retinal neurons lost due to blinding diseases.
Gene regulatory networks controlling vertebrate retinal regeneration
Science 01 Oct 2020