Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage

TLDR

A knock‑in Emx1‑IRES‑Cre mouse line was created by inserting an IRES‑Cre cassette into the Emx1 3′‑UTR, enabling Cre expression that mirrors endogenous Emx1 and permitting fate‑mapping of Emx1‑positive forebrain cells when crossed with reporter strains. Fate‑mapping shows that radial glia, Cajal‑Retzius cells, glutamatergic neurons, astrocytes, and oligodendrocytes of most pallial structures arise from Emx1‑lineage cells, whereas most pallial GABAergic neurons and some basal‑ganglia‑adjacent structures originate outside this lineage.

Abstract

By homologous recombination of an internal ribosome entry site and Cre recombinase coding region into the 3′-untranslated region of the mouse Emx1 gene, we have generated a strain of mice, Emx1^IRES^<i>cre</i>, that expresses the Cre recombinase in a spatial and temporal pattern like that observed for Emx1. When mated to reporter strains, these mice are a sensitive means to fate-map the Emx1-expressing cells of the developing forebrain. Our results demonstrate that radial glia, Cajal-Retzius cells, glutamatergic neurons, astrocytes, and oligodendrocytes of most pallial structures originate from an Emx1-expressing lineage. On the other hand, most of the pallial GABAergic neurons arise outside the Emx1-expressing lineage. Structures that are located near the basal ganglia (e.g., the amygdala and endopiriform nuclei) are not uniformly derived from Emx1-expressing cells.