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bioRxiv · 10.1101/2024.03.01.582863

Orderly specification and precise laminar deployment of cortical glutamatergic projection neuron types through intermediate progenitors

Huilgol, D.·Levine, J. M.·Galbavy, W.·Wang, B.-S.·Huang, Z. J.
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Abstract

The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the "inside-out" model whereby successive generations of PNs sequentially migrate to deep then progressively more superficial layers, but its biological significance remains unclear; and the role of iNG in this process is unknown. Using genetic strategies linking PN birth-dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviate from an inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams. HIGHLIGHTS- Each IP is fate-restricted to generate a pair of near-identical PNs - Corticogenesis involves the orderly generation of fate-restricted IP temporal cohorts - IP temporal cohorts sequentially as well as concurrently specify multiple PN types - The deployment of PN types to specific layers does not follow an inside-out order

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Huilgol, D., Levine, J. M., Galbavy, W., Wang, B.-S., Huang, Z. J.. 2024-03-02. Orderly specification and precise laminar deployment of cortical glutamatergic projection neuron types through intermediate progenitors. https://doi.org/10.1101/2024.03.01.582863

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