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Corridors of migrating neurons in the human brain and their decline during infancy

Nature volume 478, pages 382386 (20 October 2011) | Download Citation


The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb1,2,3,4,5,6. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes7. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans7. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS8,9. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports8, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb—we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.

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The authors are grateful to J. Agudelo and R. Romero for expert technical assistance and to K. X. Probst for illustrations. N.S. was supported by an NIH F32 NRSA postdoctoral fellowship (NS 058180). R.I. was supported by fellowships from the Damon Runyon Cancer Research Foundation (DRG1935-07) and American Association for Cancer Research/National Brain Tumor Society. R.A.I. thanks the American Association for Cancer Research for support. A.A.-B. is the Heather and Melanie Muss Endowed Chair of Neurological Surgery at UCSF. This work was supported by grants from the NIH (to A.A.-B., E.H. and D.H.R.), the Pediatric Brain Tumor Foundation of the United States and by the John G. Bowes Research Fund. D.H.R. is a Howard Hughes Medical Institute Investigator.

Author information


  1. Eli and Edythe Broad Institute of Regeneration Medicine and Stem Cell Research and Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143, USA

    • Nader Sanai
    • , Thuhien Nguyen
    • , Rebecca A. Ihrie
    • , Zaman Mirzadeh
    • , Hui-Hsin Tsai
    • , Michael Wong
    • , David H. Rowitch
    •  & Arturo Alvarez-Buylla
  2. Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94143, USA

    • Nader Sanai
    • , Nalin Gupta
    • , Mitchel S. Berger
    • , David H. Rowitch
    •  & Arturo Alvarez-Buylla
  3. Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, Arizona 85013, USA

    • Nader Sanai
    •  & Zaman Mirzadeh
  4. Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA

    • Eric Huang
  5. Laboratorio de Morfología Celular, Unidad Mixta CIPF-UVEG, CIBERNED, Valencia 46012, Spain

    • Jose-Manuel Garcia-Verdugo
  6. Department of Pediatrics, University of California San Francisco, San Francisco, California 94143, USA

    • David H. Rowitch


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N.S. designed the study, acquired and interpreted experimental data, and prepared the manuscript. T.N. assisted with experiments, data collection and manuscript preparation. R.A.I. designed and conducted the EGFR experiments and assisted with manuscript preparation. Z.M. designed and conducted the whole-mount experiments. H.-H.T. and M.W. conducted the in situ hybridization experiments. N.G., M.S.B. and E.H. assisted with specimen collection and neuropathological review. J.-M.G.-V. acquired and interpreted all ultrastructural analyses and assisted with study design. D.H.R. and A.A.-B. designed the study, interpreted the data and prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to David H. Rowitch or Arturo Alvarez-Buylla.

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