The determination of projection neuron identity in the developing cerebral cortex

Abstract

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.

Anatomical location of mature GnRH neurons corresponds with their birthdate in the developing mouse

“…This scenario is reminiscent of the "inside-out" pattern of neocortical development (McConnell and Kaznowski, 1991). In the developing neocortex, early-generated neurons become committed to deep layer fates by exposure to environmental factors during their final mitosis (McConnell and Kaznowski, 1991;Bohner et al, 1997;Desai and McConnell, 2000;Leone et al, 2008). Thus, by the time they migrate away from their site of differentiation, early-generated cells are committed to stopping at a particular position.…”

“…One caveat to this line of reasoning is that for neocortical projection neurons and interneurons, transplantation and fate-mapping studies indicate that the phenotype of a neuron is determined largely by the time and place of its birth (Butt et al, 2005;Miyoshi et al, 2007;Leone et al, 2008). Nevertheless, the microenvironment into which neurons, including GnRH neurons, migrate must certainly change over the migratory period as the brain develops and matures, however the identity of important factors and their exact influence on immigrating neurons is still unclear.…”

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

“…The developmental potential of forebrain cortical neuronal precursors becomes progressively restricted over time (Desai and McConnell 2000), and these cells are typically fated by signals received during a rather restricted time window around their last mitosis, within or close to the ventricular zone. Another key feature of cortical neuron development is that such fatedeWning signals can only be realized by cycling cells, and indeed cell sensitivity toward such signals varies over the cell cycle (e.g., McConnell and Kaznowski 1991;Fukumitsu et al 2006;Leone et al 2008). …”

The Basics of Brain Development

“…It appears that early in corticogenesis progenitor cells can receive signals to produce any neural cell line, but as development proceeds and these early cell types are no longer needed, the progenitor loses the capacity to generate those cells, exhibiting what is termed fate restriction. While there is evidence that fate restriction may be at least in part controlled by cell intrinsic signaling (Shen et al 2006;Leone et al 2008) the particular signaling pathways that induce these shifts in the progenitor population remain poorly defined (Molyneaux et al 2007). …”