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Math1 is essential for genesis of cerebellar granule neurons

Nature volume 390, pages 169–172 (1997)Cite this article

Abstract

The cerebellum is essential for fine motor control of movement and posture, and its dysfunction disrupts balance and impairs control of speech, limb and eye movements. The developing cerebellum consists mainly of three types of neuronal cells: granule cells in the external germinal layer, Purkinje cells, and neurons of the deep nuclei1. The molecular mechanisms that underlie the specific determination and the differentiation of each of these neuronal subtypes are unknown. Math1 (refs 2, 3), the mouse homologue of the Drosophila gene atonal4, encodes a basic helix–loop–helix transcription factor that is specifically expressed in the precursors of the external germinal layer and their derivatives. Here we report that mice lacking Math1 fail to form granule cells and are born with a cerebellum that is devoid of an external germinal layer. To our knowledge, Math1 is the first gene to be shown to be required in vivo for the genesis of granule cells, and hence the predominant neuronal population in the cerebellum.

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Figure 1: The developing cerebellum at E16.
Figure 2: Targeted disruption of the Math1 locus and generation of Math1-null mice.
Figure 3: Cerebellar abnormalities in E18.
Figure 4: Absence of the EGL in E14.
Figure 5: Inferior olive nuclei are normal in Math1 null mice.

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Acknowledgements

We thank B. A. Antalffy for technical assistance; P. R. Cox and J. Dong for their help; and R. R. Behringer, K. A. Mahon and B. Hassan for critical reading of the manuscript. H.Y.Z. is an investigator and H.J.B. is an associate investigator of the Howard Hughes Medical Institute. This work was supported by grants from the NIH/NINDS and by the Baylor Mental Retardation Research Center.

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Authors and Affiliations

  1. Departments of Molecular and Human Genetics,

    Nissim Ben-Arie, Hugo J. Bellen, Martin M. Matzuk & Huda Y. Zoghbi

  2. Pediatrics,

    Nissim Ben-Arie, Alanna E. McCall, Polina R. Gordadze & Huda Y. Zoghbi

  3. Cell Biology,

    Hugo J. Bellen & Martin M. Matzuk

  4. Pathology,

    Dawna L. Armstrong, Qiuxia Guo & Martin M. Matzuk

  5. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, 77030, Texas, USA

    Hugo J. Bellen & Huda Y. Zoghbi

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  1. Nissim Ben-Arie
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Correspondence to Huda Y. Zoghbi.

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Ben-Arie, N., Bellen, H., Armstrong, D. et al. Math1 is essential for genesis of cerebellar granule neurons. Nature 390, 169–172 (1997). https://doi.org/10.1038/36579

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