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Extrinsic Purinergic Regulation of Neural Stem/Progenitor Cells: Implications for CNS Development and Repair

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Abstract

There has been tremendous progress in understanding neural stem cell (NSC) biology, with genetic and cell biological methods identifying sequential gene expression and molecular interactions guiding NSC specification into distinct neuronal and glial populations during development. Data has emerged on the possible exploitation of NSC-based strategies to repair adult diseased brain. However, despite increased information on lineage specific transcription factors, cell-cycle regulators and epigenetic factors involved in the fate and plasticity of NSCs, understanding of extracellular cues driving the behavior of embryonic and adult NSCs is still very limited. Knowledge of factors regulating brain development is crucial in understanding the pathogenetic mechanisms of brain dysfunction. Since injury-activated repair mechanisms in adult brain often recapitulate ontogenetic events, the identification of these players will also reveal novel regenerative strategies. Here, we highlight the purinergic system as a key emerging player in the endogenous control of NSCs. Purinergic signalling molecules (ATP, UTP and adenosine) act with growth factors in regulating the synchronized proliferation, migration, differentiation and death of NSCs during brain and spinal cord development. At early stages of development, transient and time-specific release of ATP is critical for initiating eye formation; once anatomical CNS structures are defined, purinergic molecules participate in calcium-dependent neuron-glia communication controlling NSC behaviour. When development is complete, some purinergic mechanisms are silenced, but can be re-activated in adult brain after injury, suggesting a role in regeneration and self-repair. Targeting the purinergic system to develop new strategies for neurodevelopmental disorders and neurodegenerative diseases will be also discussed.

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Acknowledgments

The authors thank Dr Gillian E. Knight for her excellent editorial assistance. H.U. is grateful for grant support by from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) and CNPq (Conselho Nacional de Desenvolvimento Cientifico), Brazil. MPA is grateful to Italian Ministero dell’Università e della Ricerca (MIUR; PRIN-/COFIN program Project Prot. 2006059022 and 2008XFMEA3) and to the Fondazione Italiana Sclerosi Multipla (FISM) COD. 2010/R/2 for research support.

Conflict of interests

The authors declare that they have no competing interests or other interests that might be perceived to influence the interpretation of the article.

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Authors and Affiliations

  1. Departamento de Bioquimica, Instituto de Quimica, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, 05508-900, SP, Brazil

    Henning Ulrich

  2. Department of Pharmacological Sciences, Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, University of Milan, Via Balzaretti 9, 20133, Milan, Italy

    Maria P. Abbracchio

  3. Autonomic Neuroscience Centre, University College Medical School, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK

    Geoffrey Burnstock

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  1. Henning Ulrich
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  2. Maria P. Abbracchio
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Correspondence to Geoffrey Burnstock.

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Ulrich, H., Abbracchio, M.P. & Burnstock, G. Extrinsic Purinergic Regulation of Neural Stem/Progenitor Cells: Implications for CNS Development and Repair. Stem Cell Rev and Rep 8, 755–767 (2012). https://doi.org/10.1007/s12015-012-9372-9

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