Abstract
Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single‐cell resolution is still incomplete due to the technical variations in lineage‐tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results.
Highlights
The mammalian cerebral cortex is the outer layer of neural tissue in the telencephalon
We proposed a theoretical representation of the cell division and cell death processes operating during the neurogenic window in cerebral cortex development
We found that key limitations to our understanding of the developmental programme are the lack of characterisation of cell cycle dynamics, and the lack of identification of cell types in lineages
Summary
The mammalian cerebral cortex is the outer layer of neural tissue in the telencephalon. It is composed of a large variety of cell types (Lodato & Arlotta, 2015; Markram et al 2015; Mancinelli & Lodato, 2018; Tasic et al 2018) and shows considerable areal variation depending on the circuit elements required to perform specific computational functions (Goulas et al 2018). The location and quantity of cortical neurons are determined during embryonic development and are crucial to the emergence of cognitive functions in the adult brain. The developmental programme leading to the formation of the cerebral cortex is the result of a complex regulation of cellular processes in space and time, involving a variety of progenitor cell types (Fig. 1)
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