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, 18 (1), 28-35

The Determination of Projection Neuron Identity in the Developing Cerebral Cortex


The Determination of Projection Neuron Identity in the Developing Cerebral Cortex

Dino P Leone et al. Curr Opin Neurobiol.


Here we review the mechanisms that determine projection neuron identity during cortical development. Pyramidal neurons in the mammalian cerebral cortex can be classified into two major classes: corticocortical projection neurons, which are concentrated in the upper layers of the cortex, and subcortical projection neurons, which are found in the deep layers. Early progenitor cells in the ventricular zone produce deep layer neurons that express transcription factors including Sox5, Fezf2, and Ctip2, which play important roles in the specification of subcortically projecting axons. Upper layer neurons are produced from progenitors in the subventricular zone, and the expression of Satb2 in these differentiating neurons is required for the formation of axonal projections that connect the two cerebral hemispheres. The Fezf2/Ctip2 and Satb2 pathways appear to be mutually repressive, thus ensuring that individual neurons adopt either a subcortical or callosal projection neuron identity at early times during development. The molecular mechanisms by which Satb2 regulates gene expression involves long-term epigenetic changes in chromatin configuration, which may enable cell fate decisions to be maintained during development.


Figure 1
Figure 1. Gene expression patterns in the developing cerebral cortex during mid-neurogenesis and early postnatal life
Summary of the expression patterns of the T-box transcription factor Tbr1, the non-coding RNA Svet1, the cut-like transcription factors Cux-1 and Cux-2, the zinc-finger transcription factors Fezf2 and Ctip2, the chromatin remodeling protein Satb2, and the SRY-box transcription factor Sox5 during embryonic and early postnatal development in the mouse. Note that many of these genes show dynamic expression patterns (particularly in postnatal life) that are not fully summarized here, and that the protein expression patterns of some are more restricted compared to those of the corresponding mRNAs. Abbreviations: MZ, marginal zone; CP, cortical plate; SP, subplate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone.
Figure 2
Figure 2. A working model for the specification of callosal vs. subcortical projection neuron identity during the development of the cerebral cortex
This model is based on genetic (rather than biochemical) studies, which suggest that Fezf2 acts upstream of Ctip2 and that both play essential roles in the specification of subcortical projection neuron fates. Satb2 is required for the development of callosal projection neurons and represses the expression of Ctip2 in these cells. In the absence of Satb2, callosal projection neurons extend axons subcortically. Conversely, in the absence of Fezf2, Satb2 expression is derepressed, enabling cells to take on a callosal projection neuron fate.

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