Asymmetric Inheritance of Radial Glial Fibers by Cortical Neurons

Abstract

Recent studies demonstrated the neuronogenic role of radial glial cells (RGCs) in the rodent. To reveal the fate of radial glial processes, we intensively monitored divisions of RGCs in DiI-labeled slices from the embryonic day 14 mouse cortex. During RGC division, each pia-connected fiber becomes thin but is neither lost nor divided; it is inherited asymmetrically by one daughter cell. In divisions that produce a neuron and a progenitor, the neuron inherits the pial fiber, also grows a thick ventricular process for several hours, and is therefore indistinguishable from the progenitor RGC. The ventricular process in the radial glial-like neuron ("radial neuron") then collapses, leading to ascent of the neuron by using the "recycled" radial fiber.

The determination of projection neuron identity in the developing cerebral cortex

“…At the onset of neurogenesis, most cell divisions in the VZ are asymmetric, with one daughter cell remaining in the VZ and the other cell exiting this zone to differentiate. Several imaging studies suggest that daughter cell fates may be regulated by the asymmetric inheritance of determinants associated with the apical membrane of the progenitor cell, such that the daughter cell that inherits this domain retains a progenitor cell fate [24][25][26][27]. At mid-to late stages of neurogenesis, the outcomes of VZ cell divisions undergo a fundamental alteration.…”

Neuronal stem cells in the central nervous system and in human diseases

“…Whole-cell patch-clamp recordings with single-cell dye labeling have revealed the morphology and measured the membrane properties of randomly chosen cells in contact with the ventricular surface, suggesting that cells with the characteristic morphological features of RG cells have the physiological features of precursor cells (LoTurco et al, 1991;Noctor et al, 2002). Similarly, the application of DiI or fluorescent microbeads to the pial surface of developing neocortex labels mitotically active VZ cells with distinct RG morphology (Malatesta et al, 2000;Miyata et al, 2001), and has demonstrated that these cells constitute more than 90% of mitotically active cells in the VZ (Noctor et al, 2002(Noctor et al, , 2004.…”

“…Through lineage studies using retroviruses in chick and rodent telencephalons, radial glia and neurons are suggested to be lineally related (Gray and Sanes, 1992;Halliday and Cepko, 1992), whereas solid studies have confirmed that rodent RG cells act as neural precursor cells (Malatesta et al, 2000;Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2004Tamamaki et al, 2001). The vast majority of dividing cells in the neocortical VZ, either in the S-phase or in the M-phase, express RG markers.…”

“…Together with the observation that RG cells are the only mitotic cells in radial clones consisting of neurons and radial glia, this finding confirms that radial glia generates neurons in vivo. Furthermore, this cell type may represent the predominant neural precursor within the VZ of the developing neocortex (Malatesta et al, 2000;Miyata et al, 2001;Noctor et al, 2001Noctor et al, , 2004Tamamaki et al, 2001).…”

“…IPC then divides symmetrically to generate two neurons or two additional IPCs (Wu and Cepko, 1993;Haubensak et al, 2004;Miyata et al, 2004;Noctor et al, 2004Noctor et al, , 2007a. Therefore, embryonic SVZ is increasingly considered as a major site of neurogenesis, whereas symmetric division is recognized to transit amplifying division (Miyata et al, 2001(Miyata et al, , 2004Tarabykin et al, 2001;Smart et al, 2002;Nieto et al, 2004;Noctor et al, 2004Noctor et al, , 2007bZimmer et al, 2004;Martínez-Cerdeño et al, 2006).…”