Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo

Abstract

In the developing cerebral cortex, cell-extrinsic and cell-intrinsic signals govern the establishment of neuron subtype-specific identity. Here we show that, within the niche of the striatum, the expression of a single transcription factor, Fezf2, is sufficient to generate corticofugal neurons from progenitors fated to become medium spiny neurons. This demonstrates that a specific population of cortical projection neurons can be directed to differentiate outside of the cortex by cell-autonomous signaling.

Figure 1

LGE progenitors generate neurons with corticofugal molecular properties in response to Fezf2. Fezf2^GFP-expressing neurons located in the striatum express SOX5, TBR1, BHLHB5 and ZFPM2 (arrows), which are absent from the contralateral striatum (arrowheads). Ctx, cortex; LV, lateral ventricle; Str, striatum; CC, corpus callosum. Scale bars, 500 μm.

Figure 2

Fezf2^GFP-electroporated neurons do not express markers of MSN. (a) Coronal sections from contralateral and Fezf2^GFP-electroporated striatum showing absence of Meis2, Islet1 and Drd2 from TBR1-expressing CFu neurons. (b) Fezf2^GFP-expressing neurons do not express Gad67 (consecutive sections). Ctx, cortex; LV, lateral ventricle; Str, striatum; CC, corpus callosum. Scale bars, 500 μm and, in magnifications of boxed areas, 100 μm.

Figure 3

Fezf2 instructs the generation of CFu neurons from LGE progenitors without expression of cortical progenitor-specific genes. (a) Consecutive coronal sections showing that Fezf2^GFP-expressing LGE progenitors do not express Ngn2. (b,c) Confocal analysis showing that Fezf2^GFP-expressing LGE progenitors do not express PAX6 and TBR2. Ctx, cortex; LV, lateral ventricle; Sept, septum. Scale bars, 500 μm and, in magnifications of boxed areas, 100 μm.