Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells

Abstract

At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of Drosophila neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve a change in cleavage plane orientation from perpendicular (vertical cleavage) to parallel (horizontal cleavage) relative to the apical surface of the neuroepithelium. Here, we report, using TIS21-GFP knock-in mouse embryos to identify neurogenic neuroepithelial cells, that at the onset as well as advanced stages of neurogenesis the vast majority of neurogenic divisions, like proliferative divisions, show vertical cleavage planes. Remarkably, however, neurogenic divisions of neuroepithelial cells, but not proliferative ones, involve an asymmetric distribution to the daughter cells of the apical plasma membrane, which constitutes only a minute fraction (1-2%) of the entire neuroepithelial cell plasma membrane. Our results support a novel concept for the cell biological basis of asymmetric, neurogenic divisions of neuroepithelial cells in the mammalian central nervous system.

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.…”

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…Initial studies in the ferret CNS supported such a model; notch was shown to be located apically and stem cells dividing with a vertical cleavage plane (which will split apical determinants equally between the daughter cells) generated two stem cells while horizontal cleavage planes generated a neuronal precursor and one stem cell (Chenn and McConnell, 1995). While subsequent work has shown the number of horizontal divisions to be far too few to account for the degree of neurogenesis (Smart, 1973;Landrieu and Goffinet, 1979;Chenn and McConnell, 1995;Heins et al, 2001;Haydar et al, 2003) elegant studies from Huttner and colleagues have shown that it is the distribution of the very small apical plasma membrane which is the determinant in the control of symmetrical versus asymmetrical division (Kosodo et al, 2004;Gotz and Huttner, 2005). A cell whose cleavage plane bissects the apical plasma membrane undergoes symmetric division, while a cell whose cleavage plane still appears to be vertical but bypasses the apical plasma membrane undergoes asymmetric division.…”

“…A cell whose cleavage plane bissects the apical plasma membrane undergoes symmetric division, while a cell whose cleavage plane still appears to be vertical but bypasses the apical plasma membrane undergoes asymmetric division. Consequently, the model in which cleavage plane regulates fate appears to be correct; it is just that in the vertebrate CNS, the putative fate determinants are so restricted in location that very small changes in cleavage plane are sufficient to change fate (Kosodo et al, 2004;Gotz and Huttner, 2005). Small perturbations in cleavage plane secondary to centrosome abnormalities could, therefore, dramatically alter the ratio of symmetric and asymmetric divisions, thus generating large changes in final cell number as seen in the disorders of brain size.…”

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

“…It is also named prominin-1 for its prominent location on the protrusion of cell membranes and was the first gene identified in those for a class of novel pentaspan transmembrane glycoproteins. Although it was initially Da Cruz Paula et al: Phenotypic Heterogeneity of Breast Cancer Stem Cells (Review) considered to be a marker of hematopoietic stem cells, CD133 mRNA transcript is also found in normal nonlymphoid hematopoietic tissue (60) and has been shown to play a role in SC migration and asymmetric division (61). CD133 was reported to be overexpressed in several solid tumors (62,63), including colon cancer and glioblastoma (64,65).…”