Abstract
Indirect neurogenesis, during which neural stem cells generate neurons through intermediate progenitors, drives the evolution of lissencephalic brains to gyrencephalic brains. The mechanisms that specify intermediate progenitor identity and that regulate stem cell competency to generate intermediate progenitors remain poorly understood despite their roles in indirect neurogenesis. Well-characterized lineage hierarchy and available powerful genetic tools for manipulating gene functions make fruit fly neural stem cell (neuroblast) lineages an excellent in vivo paradigm for investigating the mechanisms that regulate neurogenesis. Type II neuroblasts in fly larval brains repeatedly undergo asymmetric divisions to generate intermediate neural progenitors (INPs) that undergo limited proliferation to increase the number of neurons generated per stem cell division. Here, we review key regulatory genes and the mechanisms by which they promote the specification and generation of INPs, safeguarding the indirect generation of neurons during fly larval brain neurogenesis. Homologs of these regulators of INPs have been shown to play important roles in regulating brain development in vertebrates. Insight into the precise regulation of intermediate progenitors will likely improve our understanding of the control of indirect neurogenesis during brain development and brain evolution.
Highlights
There is no direct correlation between neocortex size and cognitive abilities, expansion of the neocortex provides a basis for drastically increased cognitive abilities during primate brain evolution [1]
Researchers have uncovered many many mechanisms that enable stemto cells to properly exit from stemness and commechanisms that enable neuralneural stem cells properly exit from stemness and commit to differentiation
It is unclear whether the spatial organization and migration of radial glia during division—which are important in mammalian neurogenesis—are a conserved feature of Drosophila neurogenesis
Summary
There is no direct correlation between neocortex size and cognitive abilities, expansion of the neocortex provides a basis for drastically increased cognitive abilities during primate brain evolution [1]. The timely downregulation of Notch signaling activity at the transcriptional, translational, and and post-translational post-translational levels levels and and the translational, the robust robust commitment commitment to to intermediate intermediate progenitor of of neurons required for for the the proper establishment progenitor identity identityensure ensurethe thegeneration generation neurons required proper establishof neuronal circuits during the neurogenic period. Regulation of this critical transition ment of neuronal circuits during the neurogenic period. Age, and a robust in vivo platform for validating gene functions with high specificity
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