BMP controls nitric oxide-mediated regulation of cell numbers in the developing neural tube

Traister, Alexandra; Abashidze, Soulico; Gold, Veronica; Yairi, R; Michael, E; Plachta, Nicolas; McKinnell, Iain W.; Patel, Ketan; Fainsod, Abraham; Weil, Miguel

doi:10.1038/sj.cdd.4401404

Cited by 16 publications

(14 citation statements)

References 38 publications

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“…In mammalian brain, NO may regulate neural progenitor proliferation and differentiation by acting in a positive feedback loop with BDNF [22]. Most recently, it was reported that BMP4 regulate cell numbers in the developing neural tube in a NO dependent manner [113]. Consistent with this finding, an independent study reported that inhibition of nitric oxide synthesis using NOS inhibitors results in increased proliferation of precursors isolated from postnatal mouse SVZ [78].…”

Section: Embryonic Stem Cell Based Therapies For Neurodegenerative DImentioning

confidence: 77%

NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

Madhusoodanan

Murad

2006

Neurochem Res

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Nitric oxide (NO) is a short lived diatomic free radical species synthesized by nitric oxide synthases (NOS). The physiological roles of NO depend on its local concentrations as well as availability and the nature of downstream target molecules. At low nanomolar concentrations, activation of soluble guanylyl cyclase (sGC) is the major event initiated by NO. The resulting elevation in the intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse cellular and physiological processes. The participation of NO and cGMP in diverse physiological processes is made possible through cell type specific spatio-temporal regulation of NO and cGMP synthesis and signal diversity downstream of cGMP achieved through specific target selection. Thus cyclic GMP directly regulates the activities of its downstream effectors such as Protein Kinase G (PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide phosphodiesterases, which in turn regulate the activities of a number of proteins that are involved in regulating diverse cellular and physiological processes. Localization and activity of the NO-cGMP signaling pathway components are regulated by G-protein coupled receptors, receptor and non receptor tyrosine kinases, phosphatases and other signaling molecules. NO also serves as a powerful paracrine factor. At micromolar concentrations, NO reacts with superoxide anion to form reactive peroxinitrite, thereby leading to the oxidation of important cellular proteins. Extensive research efforts over the past two decades have shown that NO is an important modulator of axon outgrowth and guidance, synaptic plasticity, neural precursor proliferation as well as neuronal survival. Excessive NO production as that evoked by inflammatory signals has been identified as one of the major causative reasons for the pathogenesis of a number of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases. Regenerative therapies involving transplantation of embryonic stem cells (ES cells) and ES cell derived lineage committed neural precursor cells have recently shown promising results in animal models of Parkinson disease (PD). Recent studies from our laboratory have shown that a functional NO-cGMP signaling system is operative early during the differentiation of embryonic stem cells. The cell type specific, spatio-temporally regulated NO-cGMP signaling pathways are well suited for inductive signals to use them for important cell fate decision making and lineage commitment processes. We believe that manipulating the NO-cGMP signaling system will be an important tool for large scale generation of lineage committed precursor cells to be used for regenerative therapies.

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Section: Embryonic Stem Cell Based Therapies For Neurodegenerative DImentioning

confidence: 77%

NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

Madhusoodanan

Murad

2006

Neurochem Res

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“…The role of BMP signaling has been described in the regulation of cell numbers in the case of hematopoietic stem cells, the other subpopulation of stem cells in the bone marrow [20]. The role of BMP pathway as a cell number regulator has been described even in other systems, such as the chick developing neural tube [21]. In addition, a study indicating a relation between both stem cells populations in the bone marrow niche via BMP signaling has been published [22].…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Protein Signaling Is Involved in Human Mesenchymal Stem Cell Survival in Serum-Free Medium

Solmesky

Abekasis

Bulvik

et al. 2009

Stem Cells and Development

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Bone marrow human mesenchymal stem cells (hMSCs) are known to survive in serum-free media, when most normal somatic cells do not survive. We found that the endogenously-activated bone morphogenetic protein (BMP) pathway is involved in this cellular behavior. Under this culture condition, phosphorylated Smad1 (PSmad1), the transducer of this signal, is localized in the hMSC nuclei. In addition, inhibition of this pathway with noggin, a BMP antagonist, elicits a caspase-dependent hMSC's death in a concentration-dependent manner. Furthermore, exogenously added BMP4 alleviates the noggin effect, restoring cell survival, and suggesting that BMP signal is essential for hMSC survival under serum deprivation conditions. Altogether these findings demonstrate for the first time an endogenous survival pathway of hMSCs driven by a BMP signal. Such a survival mechanism might be involved in the maintenance of the hMSC population within their bone marrow niche.

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“…A neurogenetic role for NO has been also described in chicken during development of the neural tube, where NO is involved in the regulation of the balance between cell cycle progression and apoptotic elimination which determines the final size of neural population [39]. From these studies, it appears that NO interacts with other factors involved in the regulation of neurogenesis of the neural tube, with an action in line with its anti-proliferative role [40,41].…”

Section: Nitric Oxide and Neuronal Precursor Proli-feration During Dementioning

confidence: 91%

Nitric Oxide Control of Proliferation in Nerve Cells and in Tumor Cells of Nervous Origin

Pena-Altamira¹,

Petazzi²,

Contestabile

2010

CPD

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Recent evidence suggests that nitric oxide (NO) has a remarkable anti-proliferative action towards dividing neural precursor cells as well as towards cells giving rise to neural-derived tumors. The present paper summarizes essential literature-derived information on this issue and provides novel experimental evidence for these NO-mediated actions regarding a well characterized population of neuronal precursors, the cerebellar granule cell precursors and a cell line of medulloblastoma, a pediatric tumor originating from these same precursor cells undergoing deregulated proliferation. Evidence is presented regarding the NO-mediated regulation of proliferation of neuronal precursor cells both during developmental and adult neurogenesis. Then, the role of NO in the control of proliferation of neural-derived tumor cells, such as PC12 and neuroblastoma cells, is discussed. Novel experimental data are provided documenting the anti-proliferative action of NO towards basal and mitogen-stimulated division of rat cerebellar granule cell precursors, as well as towards medulloblastoma DAOY cells. Finally, some molecular correlates of NO action on cell cycle regulation are discussed. Overall, the data presented and discussed here highlight similarities at the molecular level between physiologic processes regulating normal proliferation of neural precursors and pathologic deregulation of these processes leading to tumor formation.

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BMP controls nitric oxide-mediated regulation of cell numbers in the developing neural tube

Cited by 16 publications

References 38 publications

NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

Bone Morphogenetic Protein Signaling Is Involved in Human Mesenchymal Stem Cell Survival in Serum-Free Medium

Nitric Oxide Control of Proliferation in Nerve Cells and in Tumor Cells of Nervous Origin

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