A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture

Abstract

The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modeling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.

Extrinsic Activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity

“…For example, vertebrate retinal progenitor cells use an intrinsic tTF cascade to bias young and old retinal fates (Elliott et al, 2008;Mattar et al, 2015). tTF series also seem to exist in cortical radial glia progenitors and even in the nerve cord (Delile et al, 2019;Gao et al, 2014;Llorca et al, 2019;Telley et al, 2016Telley et al, , 2019. Recent results also show the importance of post-transcriptional regulation in defining either young or old cortical fates (Shu et al, 2019;Zahr et al, 2018), which can be compared to the use of posttranscriptional regulators that are a hallmark of neuronal temporal patterning in Drosophila central brain neuroblasts.…”

Neurogenesis and Specification of Retinal Ganglion Cells

“…This model could explain why all retinal cell types can be generated at any given developmental time but with a different probability, ending up with RGCs generated mostly early on and rod photoreceptors later. This stochastic model is possibly a general rule for the development of the central nervous system, as suggested by recent data on the neurogenesis of the cerebral cortex [217]. The extrinsic and intrinsic factors that regulate the cell fate determination are being isolated, with compelling evolutionary conserved factors initially identified in the more deterministic neurogenesis of the drosophila eye.…”

Cell Progeny in the Olfactory Bulb after Targeting Specific Progenitors with Different UbC-StarTrack Approaches

“…The heterogeneity of NSC pools is an issue that has yet to be resolved [20,38]. The past two decades have witnessed an accumulation of abundant evidence regarding such heterogeneity, not only in the OB, but also in the dorsal cortex [39], hippocampus [40], and cerebellum [30]. Moreover, recent data show the bipotent capacity of postnatal NSCs to generate OB interneurons and glia in the cortex and striatum [21].…”