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

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The cerebral cortex develops glutamatergic projection neurons (PNs) from radial glial progenitors (RGs) via direct (dNG) or indirect neurogenesis (iNG) through intermediate progenitors (IPs).
• The established "inside-out" model posits sequential PN migration to progressively superficial cortical layers.
• The biological significance of this model and the role of iNG remain largely undetermined.

Purpose of the Study:

• To investigate the laminar deployment of IP-derived PNs in the mouse cerebral cortex.
• To determine if iNG adheres to the "inside-out" model of corticogenesis.
• To elucidate the role of iNG in the assembly of cortical circuits.

Main Methods:

• Utilized genetic strategies in mice to link PN birth dating with projection mapping.
• Employed lineage tracing and temporal analysis of PN generation and migration.
• Combined birth dating with in vivo projection analysis to track neuronal fates.

Main Results:

• The laminar positioning of IP-derived PNs significantly deviates from a strict "inside-out" pattern.
• PNs fated for non-adjacent layers were generated concurrently.
• Different PN types within the same layer were generated at non-sequential times.
• iNG facilitates the sequential specification and precise laminar placement of projection-defined PN types.

Conclusions:

• Indirect neurogenesis challenges the conventional "inside-out" model of corticogenesis.
• iNG plays a crucial role in the orderly assembly of specific cortical output channels.
• The precise laminar deployment of projection neuron types via iNG contributes to functional cortical stream organization.