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. 2025 Jul 21;60(14):1947-1957.e3.
doi: 10.1016/j.devcel.2025.02.009. Epub 2025 Mar 10.

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

Dhananjay Huilgol  1 , Jesse M Levine  2 , William Galbavy  3 , Bor-Shuen Wang  4 , Z Josh Huang  5
Affiliations

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

Dhananjay Huilgol et al. Dev Cell. .

Abstract

The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis (dNG) 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 first to deep and then progressively to more superficial layers. However, 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 deviates from a stringent 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.

Keywords: fate mapping; indirect neurogenesis; intermediate progenitors; neocortex; projection neurons.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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