P27 ^KIP1 regulates neurogenesis in the rostral migratory stream and olfactory bulb of the postnatal mouse

• Type of Material: Article
• Authors: Xuekun Li, Emory University; Xiaobing Tang, Emory University; Beata Jablonska, Childrens National Health System; Adan Aguirre, Childrens National Health System; Vittorio Gallo, Childrens National Health System; Marla Luskin, Emory University
• Language: English
• Date: 2009-03-04
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2009 Society for Neuroscience.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.4051-08.2009
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 29
• Issue: 9
• Start Page: 2902
• End Page: 2914
• Grant/Funding Information: This work was supported by National Institute of Deafness and Other Communicative Disorders Grant R01 DC03190 (M.B.L.) and National Institute of Neurological Disorders and Stroke Grants R01 NS045702 (V.G.) and K99 NS057944 (A.A.).
• Keywords: Cell Proliferation; Mesencephalon; In Situ Nick-End Labeling; Animals; Bromodeoxyuridine; Cell Movement; Olfactory Bulb; Cyclin-Dependent Kinase Inhibitor p27; Mice, Knockout; Mice; Blotting, Western; CDC2 Protein Kinase; Animals, Newborn; Nerve Tissue Proteins; Nuclear Proteins; Immunohistochemistry; Cell Survival; Antimetabolites
• Research Categories: Health Sciences, Nursing; Biology, Neuroscience

Abstract

Neuronal progenitor cells of the anterior subventricular zone (SVZa) migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they exit the cell cycle and differentiate. The molecular mechanisms that regulate SVZa progenitor proliferation and cell-cycle exit are largely undefined. We investigated the role of p27 KIP1 in regulating cell proliferation and survival in the RMS and olfactory bulb between postnatal day 1 (P1) and P14, the peak period of olfactory bulb neuron generation. A large proportion of cells in the RMS and the olfactory bulb express cytoplasmic p27 KIP1, but a small percentage display high nuclear p27 KIP1 immunostaining, which exhibit a caudal low -rostral high gradient: lowest in the SVZa and highest in the glomerular layer of the olfactory bulb. p27 KIP1 is also present in the nucleus and/or the cytoplasm of neuron-specific type III β-tubulin(+) cells. Cells with strong nuclear p27 KIP1 expression are BrdU( - ) and Ki67( - ). The percentage of BrdU( + ) cells in the SVZa, RMS, and olfactory bulb is higher in p27 KIP1 null than wild-type (WT) mice at all ages analyzed. Consistent with these findings, p27 KIP1 overexpression in cultured p27 KIP1 null and WT SVZ cells reduced cell proliferation and self-renewal. Finally, in p27 KIP1 null mice, the diameter of the horizontal limb of the RMS is larger than in WT mice, and development of the olfactory bulb granule cell layer is delayed, together with increased apoptotic cell density. Our results indicate that in the postnatal brain, p27 KIP1 regulates the proliferation and survival of neuronal cells in the RMS and olfactory bulb.