Regulation of cyclin dependent kinase inhibitor proteins during neonatal cerebella development

Watanabe, Genichi; Peña, Pilar de la; Shambaugh, George E.; Haines, G. Kenneth; Pestell, Richard G.

doi:10.1016/s0165-3806(98)00032-7

Cited by 35 publications

(31 citation statements)

References 57 publications

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“…Even GCPs from the p27−/ − mice ultimately exited the cell cycle and differentiated into mature granule cells, indicating that p27 is not the sole component of the stopping mechanism. In this study, we confirmed the previous finding that cyclin D1 is dismantled in mature granule cells (10,11), so it is likely that the absence of cyclin D1, together with the presence of p27, prevents mature granule cells from reentering the cell cycle. Huard and colleagues (12) reported that the number of granule cells was reduced in cerebella from mice lacking cyclin D2 and suggested that cyclin D2 is required for GCP proliferation.…”

Section: Introductionsupporting

confidence: 91%

Control of Proliferation and Differentiation of Neural Precursor Cells: Focusing on the Developing Cerebellum

Ishizaki¹

2006

J Pharmacol Sci

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Abstract. During CNS development, multipotent neural stem cells give rise first to various kinds of specified precursor cells, which proliferate extensively before terminally differentiating into either neurons or glial cells. Control of proliferation of the precursor cells plays a crucial role in determining the number of cells in the CNS. Proliferation is driven by mitogens, but how it is terminated remains a mystery. We examined the role of p27 / Kip1 (p27), a cyclin-dependent kinase inhibitor, in the control of proliferation of cerebellar granule cell precursors (GCPs). We found that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism. It is still not clear either whether the specified precursor cells are irreversibly determined to differentiate into their particular cell types. We examined the developmental plasticity of GCPs in vitro and found that at least some GCPs are not irreversibly committed to neuronal development but can be induced to differentiate into astroglial cells by appropriate extracellular signals.

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Section: Introductionsupporting

confidence: 91%

Control of Proliferation and Differentiation of Neural Precursor Cells: Focusing on the Developing Cerebellum

Ishizaki¹

2006

J Pharmacol Sci

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“…Cells in the deepest part of EGL, as well as in the ML and in the internal granular layer (IGL), do not express cyclin-D1, indicating their status of non-proliferating cells [119][120][121]. Thus, at the time when they are ready to leave the proliferative niche, GCPs undergo some cell-autonomous changes that are critical to exit the cell cycle.…”

Section: Shh and Granule Cellsmentioning

confidence: 99%

Sonic hedgehog patterning during cerebellar development

Luca

Cerrato

Fucà

et al. 2015

Cell. Mol. Life Sci.

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Abstract:Robust evidence in literature indicates that the morphogenic factor Sonic Hedgehog (Shh) actively orchestrates several aspects of cerebellar development and maturation. During embryogenesis Shh signalling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Purkinje cell (PC)-secreted Shh sustains the amplification of neurogenic niches active during postnatal development: the external granular layer (EGL) and the prospective white matter (PWM) where excitatory granule cells and inhibitory interneurons, respectively, are produced. In addition, Shh signalling acts on Bergmann glia differentiation and during development sustains cerebellar foliation. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying the role of this ligand in the development of different cerebellar phenotypes. Keywords: Shh, mitogen, differentiation, cerebellum.Authors declare no conflict of interest. AbstractRobust evidence in literature indicates that the morphogenic factor Sonic Hedgehog (Shh) actively orchestrates several aspects of cerebellar development and maturation. During embryogenesis Shh

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“…G1-phase-specific cyclin-dependent kinases (CDK4 and CDK6) are instrumental in the progression from G1 to S phase (Sherr, 1994 ; Hirai et al, 1995;Sherr and Roberts, 1999;Roussel, 1999). Several studies have suggested that CKIs are involved in the regulation of neurogenesis by regulating the timely withdrawal of progenitor cells from the cell cycle (Elledge and Harper, 1994;Zindy et al, 1997a,b;van Lookeren Campagne and Gill, 1998;Watanabe et al, 1998).…”

Section: Svza Neuronal Progenitor Cells Successively Undergo Rounds Omentioning

confidence: 99%

Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream

Coskun

Luskin

2002

J of Neuroscience Research

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An overriding principle of development is that neurons become permanently postmitotic once they initiate differentiation. Work in our laboratory, however, has provided evidence for a population of progenitor cells in mammalian forebrain that express properties of differentiated neurons, even though they continue to divide. These neuronal progenitor cells are situated in the rostral migratory stream (RMS), which extends from a specialized portion of the subventricular zone surrounding the anterior tip of the lateral ventricle, referred to as the SVZa, to the middle of the olfactory bulb. As SVZa‐derived cells migrate to the olfactory bulb, they undergo cell division, and they never deviate from the RMS. Once they reach their final destinations, they become terminally postmitotic interneurons. This Mini‐Review concerns findings from our recent experiments designed to reveal the intrinsic and extrinsic mechanisms governing the proliferation and differentiation of the unique SVZa neuronal progenitor cells. We have investigated the role(s) of cell cycle regulatory proteins, in particular, the cell cycle inhibitor p19INK4d, in the control of SVZa cell proliferation. Several studies have indicated that cells withdraw from the cell cycle once they express p19INK4d. To begin to investigate whether p19INK4d(+) SVZa‐derived cells are postmitotic, we analyzed the pattern of p19INK4d expression by the cells of the RMS. A pronounced gradient of p19INK4d expression was demonstrated; progressively more cells are p19INK4d immunoreactive as the olfactory bulb is approached. In addition, the capacity of p19INK4d(+) cells to incorporate bromodeoxyuridine was investigated. From the results of these studies, we conclude that SVZa cells in the RMS can successively down‐regulate their expression of p19INK4d as they migrate and that they repeatedly exit and reenter the cell cycle while en route to the olfactory bulb. These studies led us to investigate whether bone morphogenetic proteins (BMPs) are involved in the regulation of SVZa cell proliferation and p19INK4d expression, because, elsewhere in the CNS, BMPs modulate cell proliferation and influence cell fate decisions. To determine the effects of BMP signaling on SVZa cell proliferation and differentiation, we altered the expression of the BMP receptor Ia (BMPR‐Ia) using retrovirally mediated gene transfer. The cells in the SVZa encoding the wild‐type BMPR‐Ia exit the cell cycle and do not appear to migrate through the RMS. Conversely, both within the SVZa and along the RMS, the majority of SVZa‐derived cells encoding a dominant‐negative BMPR‐Ia gene do not express p19INK4d. These findings indicate that p19INK4d expression is suppressed when BMP signaling is inhibited. Furthermore, SVZa‐derived cells with both augmented and inhibited BMP signaling retain their neuronal commitment. Collectively, these studies have revealed that SVZa cell proliferation and differentiation is under the control of several interacting intrinsic and extrinsic factors. © 2002 Wiley‐Liss, Inc.

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Regulation of cyclin dependent kinase inhibitor proteins during neonatal cerebella development

Cited by 35 publications

References 57 publications

Control of Proliferation and Differentiation of Neural Precursor Cells: Focusing on the Developing Cerebellum

Control of Proliferation and Differentiation of Neural Precursor Cells: Focusing on the Developing Cerebellum

Sonic hedgehog patterning during cerebellar development

Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream

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