Abstract Neuronal plasticity can vary remarkably in its form and degree across animal species. Adult neurogenesis, namely the capacity to produce new neurons from neural stem cells through adulthood, appears widespread in non-mammalian vertebrates, whereas it is reduced in mammals. A growing body of comparative studies also report variation in the occurrence and activity of neural stem cell niches between mammals, with a general trend of reduction from small-brained to large-brained species. Conversely, recent studies have shown that large-brained mammals host large amounts of neurons expressing typical markers of neurogenesis in the absence of cell division. In layer II of the cerebral cortex, populations of prenatally generated, non-dividing neurons continue to express molecules indicative of immaturity throughout life (cortical immature neurons; cINs). After remaining in a dormant state for a very long time, these cINs retain the potential of differentiating into mature neurons that integrate within the preexisting neural circuits. They are restricted to the paleocortex in small-brained rodents, while extending into the widely expanded neocortex of highly gyrencephalic, large-brained species. The current hypothesis is that these populations of non-newly generated “immature” neurons might represent a reservoir of developmentally plastic cells for mammalian species that are characterized by reduced stem cell-driven adult neurogenesis. This indicates that there may be a trade-off between various forms of plasticity that coexist during brain evolution. This balance may be necessary to maintain a “reservoir of plasticity” in brain regions that have distinct roles in species-specific socioecological adaptations, such as the neocortex and olfactory structures.
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tec-1 kinase negatively regulates regenerative neurogenesis in planarians
Negative regulators of adult neurogenesis are of particular interest as targets to enhance neuronal repair, but few have yet been identified. Planarians can regenerate their entire CNS using pluripotent adult stem cells, and this process is robustly regulated to ensure that new neurons are produced in proper abundance. Using a high-throughput pipeline to quantify brain chemosensory neurons, we identify the conserved tyrosine kinase tec-1 as a negative regulator of planarian neuronal regeneration. tec-1RNAi increased the abundance of several CNS and PNS neuron subtypes regenerated or maintained through homeostasis, without affecting body patterning or non-neural cells. Experiments using TUNEL, BrdU, progenitor labeling, and stem cell elimination during regeneration indicate tec-1 limits the survival of newly differentiated neurons. In vertebrates, the Tec kinase family has been studied extensively for roles in immune function, and our results identify a novel role for tec-1 as negative regulator of planarian adult neurogenesis.
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- Award ID(s):
- 1764421
- PAR ID:
- 10251908
- Date Published:
- Journal Name:
- eLife
- Volume:
- 9
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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