Abstract
Cut-Like Homeobox 2 (Cux2) is a transcription factor involved in dendrite and spine development, and synapse formation of projection neurons placed in mouse upper neocortical layers. Therefore, Cux2 is often used as an upper layer marker in the mouse brain. However, expression of its orthologue CUX2 remains unexplored in the human fetal neocortex. Here, we show that CUX2 protein is expressed in transient compartments of developing neocortical anlage during the main fetal phases of neocortical laminar development in human brain. During the early fetal phase when neurons of the upper cortical layers are still radially migrating to reach their final place in the cortical anlage, CUX2 was expressed in the marginal zone (MZ), deep cortical plate, and pre-subplate. During midgestation, CUX2 was still expressed in the migrating upper cortical neurons as well as in the subplate (SP) and MZ neurons. At the term age, CUX2 was expressed in the gyral white matter along with its expected expression in the upper layer neurons. In sum, CUX2 was expressed in migratory neurons of prospective superficial layers and in the diverse subpopulation of transient postmigratory SP and MZ neurons. Therefore, our findings indicate that CUX2 is a novel marker of distinct transient, but critical histogenetic events during corticogenesis. Given the Cux2 functions reported in animal models, our data further suggest that the expression of CUX2 in postmigratory SP and MZ neurons is associated with their unique dendritic and synaptogenesis characteristics.
Highlights
In the early fetal phase, at 10 post-conceptual weeks (PCW), Cut-Like Homeobox 2 (CUX2)-protein immunopositive (CUX2+) nuclei were found during formation and first condensation of the cortical plate (CP)
Strong CUX2+ nuclei were depicted in the marginal zone (MZ), deep CP and pre-subplate (Figure 1)
At 12 PCW, CUX2+ nuclei were present in the upper third of the MZ co-localizing with
Summary
Fetal and midfetal stages of the human brain development include crucial histogenetic events resulting in the basic framework of areal, laminar, and regional organization, and connectivity [1,2] This basic framework includes formation of transient zones like subplate (SP) and marginal zone (MZ) populated by a number of diverse cells, including neurons that will form first neocortical synapses. The neurons in these transient laminar compartments have a major role in forming first neocortical connections, by providing first projections out of the neocortex and receptive fields for the ingrowing axons with their dendrites, guiding the ingrowing afferents, and forming pioneering and transient neocortical synapses.
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