Abstract
The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review article we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.
Highlights
The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers
The basal processes of Radial glia progenitors (RGPs) serve as a scaffold for nascent cortical neurons, which migrate from the ventricular zone (VZ)/subventricular zone (SVZ) through the intermediate zone (IZ), in order to reach the cortical plate (CP; Rakic, 1972; Evsyukova et al, 2013)
Newly-born cortical neurons migrate, in a step-wise fashion coupled with changes in cell polarity, from the VZ/SVZ through IZ zone in order to reach the CP where they position themselves at their final location (Figure 1; Rakic, 1972; Nadarajah and Parnavelas, 2002; Noctor et al, 2004; Tsai et al, 2005; Marín et al, 2010; Hippenmeyer, 2014)
Summary
The mammalian cerebral cortex emerges from the neuroectoderm. At the end of neurulation and neural tube closure, occurring from embryonic day (E) 7 to E9 in mice, the early neuroepithelium is composed of neuroepithelial stem cells (NESCs) from which all subsequent neural progenitor cells and their neuron lineages derive (Figure 1). NESC polarity correlates with the asymmetric distribution of cell fate determinants which are thought to control the fine balance between symmetric and asymmetric progenitor divisions (Shitamukai and Matsuzaki, 2012) Such balance is critical for the generation of the correct number of radial glia progenitor cells (RGPCs), which are lineally related to NESCs but exhibit even more polarized cellular morphology with an extended basal process (Taverna et al, 2014). It will be important to precisely dissect the sequential and/or distinct functions of proteins orchestrating cellular polarity during development
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