Our group studies the cell biological mechanisms of neurogenesis in the context of mammalian brain evolution, specifically the proliferation versus differentiation of neuroepithelial (NE) cells and their progeny. In the course of neurogenesis, mouse NE cells down-regulate a number of epithelial features. Expression of the anti-proliferative gene Tis21 can be used as a tool to distinguish between proliferating and neuron-generating NE cells. Time-lapse microscopy of neuron-generating divisions of NE cells using transgenic mouse embryos expressing GFP under the control of the Tis21 promoter reveals the existence of a novel neuronal progenitor dividing at the basal side of the neuroepithelium. To study the distribution, during mitosis, of cellular components in the context of the apico-basal axis of NE cells, we focus on prominin-1/CD133, a pentaspan membrane protein sorted to the apical surface of NE cells and specifically retained in plasma membrane protrusions. Prominin-1 is associated with a novel, cholesterol-based membrane microdomain which is involved in prominins retention in plasma membrane protrusions. Using prominin-1 to define the apical surface of NE cells, we investigate the symmetric versus asymmetric distribution of the apical plasma membrane during proliferative versus neuron-generating divisions of NE cells. Knock-down of Aspm, implicated in microcephaly, by RNA interference in the developing mouse embryo demonstrates that this mitotic spindle pole-associated protein is crucial for maintaining a cleavage plane orientation that allows symmetric, proliferative divisions of NE cells during brain development. Remarkably, preceding the switch to neurogenesis, the prominin-1containing apical plasma membrane microdomain of NE cells is released into the neural tube lumen as novel extracellular vesicles that originate from the midbody and primary cilium.
Götz & Huttner Nat Rev Mol Cell Biol 2005 6 777788.
Huttner & Kosodo Curr Opin Cell Biol 2005 17 648657.
Fish et al. PNAS 2006 103 1043810443.
Dubreuil et al. J Cell Biol 2007 176 483495.
03 - 07 May 2008
European Society of Endocrinology