Neurogenesis in the mammalian central nervous system
Previous and Current Research
CNS neurons originate from neuroepithelial cells. We study the cell biological mechanisms underlying the switch of neuroepithelial cells from proliferation to neurogenesis in the mouse embryo. Prior to, during, and as a consequence of, neurogenesis, neuroepithelial cells down-regulate a number of epithelial features. Expression of the antiproliferative gene TIS21 can be used (i) as a tool to distinguish between proliferating and neuron-generating neuroepithelial cells and (ii) as a means of imaging neuron-generating divisions of neuroepithelial cells. To study the distribution, during mitosis, of cellular components in the context of the apico-basal axis of neuroepithelial cells, we have focused on prominin, a pentaspan membrane protein identified by our group that is sorted to the apical surface of neuroepithelial cells and specifically retained in plasma membrane protrusions. Prominin is associated with a novel, cholesterol-based lipid raft.
Future Projects and Goals
Future projects concern the cell biological as well as genomic basis of neurogenesis in the mammalian central nervous system. Our goal is to elucidate, at the molecular level, the switch of neuroepithelial cells from proliferative to neuron-generating division.
Huttner WB, Kosodo Y.
Symmetric versus asymmetric cell division during neurogenesis in the developing vertebrate central nervous system.
Curr Opin Cell Biol. 2005 Dec;17(6):648-57. (2005)
Gotz M, Huttner WB.
The cell biology of neurogenesis.
Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88. Review. (2005)
Calegari F, Haubensak W, Haffner C, Huttner WB.
Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development.
J Neurosci. 2005 Jul 13;25(28):6533-8. (2005)
Marzesco AM, Janich P, Wilsch-Brauninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB
Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells.
J Cell Sci. 2005 Jul 1;118(Pt 13):2849-58. (2005)
Kosodo, Y., Röper, K., Haubensak, W., Marzesco, A. M., Corbeil, D. and Huttner, W. B.
Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells.
EMBO J., 23, 2314-2324. (2004)
Haubensak, W., Attardo, A., Denk, W. and Huttner, W. B.
Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: A major site of neurogenesis.
Proc. Natl. Acad. Sci USA, 101, 3196-32015. (2004)
Calegari, F. and Huttner, W. B.
An inhibition of cyclin-dependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis.
J. Cell Sci., 116, 4947-4955. (2003)