Cell migration in the normal and pathological postnatal mammalian brain

https://doi.org/10.1016/j.pneurobio.2009.02.001Get rights and content

Abstract

In the developing brain, cell migration is a crucial process for structural organization, and is therefore highly regulated to allow the correct formation of complex networks, wiring neurons, and glia. In the early postnatal brain, late developmental processes such as the production and migration of astrocyte and oligodendrocyte progenitors still occur. Although the brain is completely formed and structured few weeks after birth, it maintains a degree of plasticity throughout life, including axonal remodeling, synaptogenesis, but also neural cell birth, migration and integration. The subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus are the two main neurogenic niches in the adult brain. Neural stem cells reside in these structures and produce progenitors that migrate toward their ultimate location: the olfactory bulb and granular cell layer of the DG respectively. The aim of this review is to synthesize the increasing information concerning the organization, regulation and function of cell migration in a mature brain. In a normal brain, proteins involved in cell–cell or cell–matrix interactions together with secreted proteins acting as chemoattractant or chemorepellant play key roles in the regulation of neural progenitor cell migration. In addition, recent data suggest that gliomas arise from the transformation of neural stem cells or progenitor cells and that glioma cell infiltration recapitulates key aspects of glial progenitor migration. Thus, we will consider glioma migration in the context of progenitor migration. Finally, many observations show that brain lesions and neurological diseases trigger neural stem/progenitor cell activation and migration toward altered structures. The factors involved in such cell migration/recruitment are just beginning to be understood. Inflammation which has long been considered as thoroughly disastrous for brain repair is now known to produce some positive effects on stem/progenitor cell recruitment via the regulation of growth factor signaling and the secretion of a number of chemoattractant cytokines. This knowledge is crucial for the development of new therapeutic strategies. One of these strategies could consist in increasing the mobilization of endogenous progenitor cells that could replace lost cells and improve functional recovery.

Section snippets

Introduction: from development to the adult brain

The development of a structure as complex as the brain from the embryo to the adult organism is a continued source of fascination for neurobiologists. Successive, overlapping phases occur during brain development: first, the proliferation of embryonic neural stem cells in the ventricular neuroepithelium produces growth of the structure, second, a neurogenic phase takes place and gives rise to cortical neurons, third, gliogenesis occurs, and finally myelination, axon pruning, synaptic

Cell migration in the early postnatal period

An extensive amount of cell migration occurs in the first few postnatal weeks of the rodent brain. Much of this is by glial progenitors, since most neuronal migration has been completed by this time, with a few exceptions. Two of the exceptions, olfactory bulb interneuron generation in the forebrain SVZ and migration along the RMS, and dentate gyrus granule cell generation and migration in the hippocampus, continue to occur throughout adult life (see below). Another exception is the cerebellum,

Factors involved in the regulation of progenitor cell migration in the normal adult brain

A fundamental issue concerning adult migration is to understand the intrinsic and extracellular cues that allow the persistence of migratory progenitors. Increasing evidence argues for the involvement of developmental signals that are maintained in restricted adult brain structures. It thus appears that the adult brain uses developmental strategies in order to maintain a higher degree of plasticity permissive for cell remodeling. In the adult as in development, orientated neuronal migration

Psychiatric disorders

In the last few years, a number of studies have examined the impact of neurological pathologies on neurogenesis niches in the adult brain. They lead to the conclusion that cell proliferation and cell migration in the SVZ and DG are almost always disturbed in the diseased brain, including models of psychiatric disorders, neurodegenerative diseases or traumatic injuries. However, it is not clear whether these modifications of neurogenesis are the causes or the consequences of brain pathologies (

Therapeutic strategies and perspectives

Considering the migratory and potential migratory abilities of stem/progenitor cells, one could propose the mobilization of endogenous stem and progenitor cells as an alternative to grafting. Repair by endogenous cells would overcome the problem of transplant rejection. Despite its status of “immuno-privileged organ”, recent findings demonstrate that the brain remains sensitive to immune attacks via some activated lymphocytes and microglial cells with antigen presenting properties (Wekerle, 2007

Conclusion

The recent finding that neural stem cells reside in the adult central nervous system throughout life and present the capacity to migrate through this mature structure raised hope to develop new therapeutic strategies. However, the endogenous progenitor cell mobilization that spontaneously occurs after a lesion or in neurodegenerative pathologies only leads to very low rates of cell replacement. Transplantation strategies can be considered an interesting alternative since (i) white matter tracts

Glossary

Neural stem cells
Cells that reside in the neural tissue and are multipotent (can give rise to astrocytes, oligodendrocytes and neurons) and have the capacity to self renew (they divide and maintain a pool of cells identical to themselves all life long).
Neural progenitors
Derive from neural stem cells but present a restricted potentiality (often unipotent). Although they are proliferative cells, they present limited self-renewal potential. Here we used the term “neuroblast” to design a neuronal

References (352)

  • L. Decker et al.

    Oligodendrocyte precursor migration and differentiation: combined effects of PSA residues, growth factors, and substrates

    Mol. Cell. Neurosci.

    (2000)
  • F. Doetsch et al.

    Subventricular zone astrocytes are neural stem cells in the adult mammalian brain

    Cell

    (1999)
  • X. Duan et al.

    Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain

    Cell

    (2007)
  • J.G. Emsley et al.

    alpha6beta1 integrin directs migration of neuronal precursors in adult mouse forebrain

    Exp. Neurol.

    (2003)
  • A. Fahrner et al.

    Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients

    Exp. Neurol.

    (2007)
  • S.H. Fatemi

    Reelin glycoprotein in autism and schizophrenia

    Int. Rev. Neurobiol.

    (2005)
  • R. Feng et al.

    Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces

    Neuron

    (2001)
  • S.N. Fewou et al.

    Down-regulation of polysialic acid is required for efficient myelin formation

    J. Biol. Chem.

    (2007)
  • F. Francis et al.

    Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons

    Neuron

    (1999)
  • K.S. Aboody et al.

    Stem and progenitor cell-mediated tumor selective gene therapy

    Gene Therapy

    (2008)
  • A. Aguirre et al.

    A functional role for EGFR signaling in myelination and remyelination

    Nat. Neurosci.

    (2007)
  • A. Aguirre et al.

    Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors

    J. Neurosci.

    (2005)
  • J. Aicardi

    The place of neuronal migration abnormalities in child neurology

    Can. J. Neurol. Sci.

    (1994)
  • G. Alonso

    Proliferation of progenitor cells in the adult rat brain correlates with the presence of vimentin-expressing astrocytes

    Glia

    (2001)
  • M. Alonso et al.

    Turning astrocytes from the rostral migratory stream into neurons: a role for the olfactory sensory organ

    J. Neurosci.

    (2008)
  • J. Altman et al.

    Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale

    J. Comp. Neurol.

    (1990)
  • J. Altman et al.

    Development of the Cerebellar System

    (1997)
  • N. Andrade et al.

    ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in postnatal neuronal migration independently of Reelin

    Proc. Natl. Acad. Sci. U.S.A.

    (2007)
  • E. Angot et al.

    Chemoattractive activity of sonic hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb

    Stem Cells

    (2008)
  • E.S. Anton et al.

    Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain

    Nat. Neurosci.

    (2004)
  • R.C. Armstrong et al.

    Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules

    J. Neurosci. Res.

    (1990)
  • H.A. Arnett et al.

    TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination

    Nat. Neurosci.

    (2001)
  • A. Arvidsson et al.

    Neuronal replacement from endogenous precursors in the adult brain after stroke

    Nat. Med.

    (2002)
  • M. Assanah et al.

    Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses

    J. Neurosci.

    (2006)
  • A. Ayuso-Sacido et al.

    The duality of epidermal growth factor receptor (EGFR) signaling and neural stem cell phenotype: cell enhancer or cell transformer?

    Curr. Stem Cell Res. Ther.

    (2006)
  • S.A. Baker et al.

    Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone

    Eur. J. Neurosci.

    (2004)
  • F. Balordi et al.

    Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons

    J. Neurosci.

    (2007)
  • C.M. Batista et al.

    A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse

    J. Neurosci.

    (2006)
  • C. Beadle et al.

    The role of myosin ii in glioma invasion of the brain

    Mol. Biol. Cell

    (2008)
  • S. Belachew et al.

    Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons

    J. Cell. Biol.

    (2003)
  • A. Bellion et al.

    Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear

    J. Neurosci.

    (2005)
  • O. Belluzzi et al.

    Electrophysiological differentiation of new neurons in the olfactory bulb

    J. Neurosci.

    (2003)
  • A. Belmadani et al.

    Chemokines regulate the migration of neural progenitors to sites of neuroinflammation

    J. Neurosci.

    (2006)
  • K.L. Blaschuk et al.

    The regulation of proliferation and differentiation in oligodendrocyte progenitor cells by alphaV integrins

    Development

    (2000)
  • R. Belvindrah et al.

    Beta1 integrins control the formation of cell chains in the adult rostral migratory stream

    J. Neurosci.

    (2007)
  • A. Benraiss et al.

    Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain

    J. Neurosci.

    (2001)
  • P.J. Bernier et al.

    Newly generated neurons in the amygdala and adjoining cortex of adult primates

    Proc. Natl. Acad. Sci. U.S.A.

    (2002)
  • I. Blumcke et al.

    Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy

    Hippocampus

    (2001)
  • A.J. Bolteus et al.

    GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone

    J. Neurosci.

    (2004)
  • A. Borta et al.

    Dopamine and adult neurogenesis

    J. Neurochem.

    (2007)
  • Cited by (192)

    • Neuroblasts contribute to oligodendrocytes generation upon demyelination in the adult mouse brain

      2022, iScience
      Citation Excerpt :

      This suggests that an increased glycolytic activity, besides being important for cell fate reprogramming, may be a general feature of oligodendroglial cell identity acquisition (Gascon et al., 2016). In addition to altering the transcriptional state of a many SVZ NBs, demyelination signals also modify their migratory path by redirecting them toward the areas of damage and cell loss (Cayre et al., 2009; El Waly et al., 2014). Indeed, after lesion, NBs rapidly leave the RMS (Jin et al., 2003) and perform long-distance migration through the brain parenchyma (Cayre et al., 2009).

    View all citing articles on Scopus
    View full text