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Interhemispheric asymmetry of olfactory input-dependent neuronal specification in the adult brain

Nature Neuroscience volume 16, pages 884888 (2013) | Download Citation

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The vertebrate brain is anatomically and functionally asymmetric. The left and right cerebral hemispheres harbor neural stem cell niches at the ventricular-subventricular zone (V-SVZ) of the ventricular walls, where new neurons are continuously generated throughout life. However, any interhemispheric asymmetry of neural stem cell niches remains unclear. We performed gene-trap screens in adult zebrafish to identify genes that are differentially expressed in the two hemispheres and found that adult-born neurons expressing the neural zinc-finger protein Myt1 exist predominantly in the left V-SVZ. This lateralization could be reversed by left olfactory sensory deprivationinduced inactivation of Notch signaling. The olfactory behavioral preference for attractive amino acids was also impaired by sensory deprivation of the left olfactory system, but not of the right olfactory system. Our findings suggest that olfactory input generates interhemispheric differences in the fate of adult-born neurons in the zebrafish brain.

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Change history

  • 11 June 2013

    In the version of this article initially published online, two images, a figure legend and an Online Methods heading were incorrect. In Figure 3a, the Left Occlusion panel was a mirror image of the Control panel. In Figure 5a, the Control panel was a mirror image of Figure 1e, center panel. (All quantitative analyses were performed on the correct images, so these errors do not affect the conclusions of the article.) Figure 6c was described as retrograde labeling from the olfactory bulb; it shows anterograde labeling from the left olfactory bulb. And an Online Methods section was entitled “Labeling of habenular efferent projections”; the correct title is “Anterograde DiI labeling from the olfactory bulb.” The errors have been corrected for the print, PDF and HTML versions of this article.


  1. 1.

    , & Adult neural stem cells bridge their niche. Cell Stem Cell 10, 698–708 (2012).

  2. 2.

    , & Adult neurogenesis and functional plasticity in neuronal circuits. Nat. Rev. Neurosci. 7, 179–193 (2006).

  3. 3.

    et al. From the olfactory bulb to higher brain centers: genetic visualization of secondary olfactory pathways in zebrafish. J. Neurosci. 29, 4756–4767 (2009).

  4. 4.

    et al. Genetic dissection of neural circuits by Tol2 transposon–mediated Gal4 gene and enhancer trapping in zebrafish. Proc. Natl. Acad. Sci. USA 105, 1255–1260 (2008).

  5. 5.

    et al. A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. Dev. Cell 7, 133–144 (2004).

  6. 6.

    et al. Olfactory neural circuitry for attraction to amino acids revealed by transposon-mediated gene trap approach in zebrafish. Proc. Natl. Acad. Sci. USA 106, 9884–9889 (2009).

  7. 7.

    et al. Migration of neuronal precursors from the telencephalic ventricular zone into the olfactory bulb in adult zebrafish. J. Comp. Neurol. 519, 3549–3565 (2011).

  8. 8.

    et al. X-MyT1, a Xenopus C2HC-type zinc finger protein with a regulatory function in neuronal differentiation. Cell 87, 1191–1202 (1996).

  9. 9.

    , & Multiple regulatory elements with spatially and temporally distinct activities control neurogenin1 expression in primary neurons of the zebrafish embryo. Mech. Dev. 120, 211–218 (2003).

  10. 10.

    , & Proneural genes and the specification of neural cell types. Nat. Rev. Neurosci. 3, 517–530 (2002).

  11. 11.

    et al. Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells. J. Neurosci. 30, 7961–7974 (2010).

  12. 12.

    & A cluster of non-redundant Ngn1 binding sites is required for regulation of deltaA expression in zebrafish. Dev. Biol. 350, 198–207 (2011).

  13. 13.

    , , & Temporally regulated asymmetric neurogenesis causes left-right difference in the zebrafish habenular structures. Dev. Cell 12, 87–98 (2007).

  14. 14.

    , , & Nodal signaling imposes left-right asymmetry upon neurogenesis in the habenular nuclei. Development 136, 1549–1557 (2009).

  15. 15.

    et al. The habenula is crucial for experience-dependent modification of fear responses in zebrafish. Nat. Neurosci. 13, 1354–1356 (2010).

  16. 16.

    et al. Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors. Proc. Natl. Acad. Sci. USA 105, 19498–19503 (2008).

  17. 17.

    The Zebrafish Book (University of Oregon Press, 1995).

  18. 18.

    , , , & Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253–310 (1995).

  19. 19.

    , & Neuronal regeneration in a zebrafish model of adult brain injury. Dis. Model. Mech. 5, 200–209 (2012).

  20. 20.

    , , & An instructive function for Notch in promoting gliogenesis in the zebrafish retina. Development 128, 1099–1107 (2001).

  21. 21.

    Deafferentation-induced changes in the olfactory bulb of adult zebrafish. Brain Res. 866, 92–100 (2000).

  22. 22.

    & Behavioral responses of newly hatched zebrafish (Danio rerio) to amino acid chemostimulants. Chem. Senses 29, 93–100 (2004).

  23. 23.

    & Cerebroventricular microinjection (CVMI) into adult zebrafish brain is an efficient misexpression method for forebrain ventricular cells. PLoS ONE 6, e27395 (2011).

  24. 24.

    et al. Asymmetric nodal signaling in the zebrafish diencephalon positions the pineal organ. Development 127, 5101–5112 (2000).

  25. 25.

    et al. Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus. Curr. Biol. 15, 238–243 (2005).

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We thank T. Seki (Tokyo Medical University) for the antibody to PSA-NCAM, U. Strähle (Karlsruhe Institute of Technology) for the Tg(neurog1:gfp) fish, A. Alvarez-Buylla and Y. Yoshihara for helpful comments on the manuscript, and members of the Sawamoto laboratory for discussions. This work was supported by the Funding Program for Next Generation World-Leading Researchers from the Japan Society for the Promotion of Science (LS104 to K.S.), the National BioResource Project (K.K.), a Grant-in-Aid for Scientific Research (C) (20509005 to N.K.) and a Grant-in-Aid for Scientific Research (A) (23241063 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology.

Author information


  1. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

    • Norihito Kishimoto
    •  & Kazunobu Sawamoto
  2. Division of Molecular and Developmental Biology, National Institute of Genetics, and Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka, Japan.

    • Kazuhide Asakawa
    •  & Koichi Kawakami
  3. Université de Toulouse, UPS, Centre de Biologie du Développement, Toulouse, France.

    • Romain Madelaine
    •  & Patrick Blader
  4. Centre National de la Recherche Scientifique, Centre de Biologie du Développement, UMR 5547, Toulouse, France.

    • Romain Madelaine
    •  & Patrick Blader


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N.K. collected most of the data. N.K. and K.S. wrote the manuscript. K.A., R.M., P.B. and K.K. generated transgenic fish.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kazunobu Sawamoto.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–6


  1. 1.

    Supplementary Movie 1

    GFP-expressing cells migrate toward the olfactory bulb in the adult SAGFF31B brain. Time-lapse video imaging of the GFP+ cells moving in the RMS, recorded at 15-minute intervals for 20 hours. GFP+ cells migrated toward the olfactory bulb at 35 ± 3 μm/h (n=30 cells from 3 animals, P<0.001).

  2. 2.

    Supplementary Movie 2

    The attraction response to amino acids of adult wild-type zebrafish.

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