Presenilins are required for maintenance of neural stem cells in the developing brain

Molecular Neurodegeneration
Woo-Young Kim, Jie Shen

Abstract

The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO) mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC) or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11). In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes...Continue Reading

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Citations

Nov 6, 2003·Journal of Chemical Neuroanatomy·Alexander StorchJohannes Schwarz
Aug 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bei WuJie Shen
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Methods Mentioned

BETA
transgenic
dissection
electrophoresis
PCR

Software Mentioned

Primer Express
Excel
LSM 510

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