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Neuronal position in the developing brain is regulated by mouse disabled-1

Abstract

During mammalian brain development, immature neurons migrate radially from the neuroectoderm to defined locations, giving rise to characteristic cell layers1,2. Here we show that targeted disruption of the mouse disabled1 ( mdab1 ) gene3 disturbs neuronal layering in the cerebral cortex, hippocampus and cerebellum. The gene encodes a cytoplasmic protein, mDab1 p80, which is expressed and tyrosine-phosphorylated in the developing nervous system3. It is likely to be an adaptor protein, docking to others through its phosphotyrosine residues and protein-interacting domain4. The mdab1 mutant phenotype is very similar to that of the reeler mouse5,6,7. The product of the reeler gene, Reelin, is a secreted protein that has been proposed to act as an extracellular signpost for migrating neurons8,9,10. Because mDab1 is expressed in wild-type cortical neurons, and Reelin expression is normal in mdab1 mutants, mDab1 may be part of a Reelin-regulated or parallel pathway that controls the final positioning of neurons.

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Figure 1: Disruption of the mdab1 gene.
Figure 2: Alterations in the mdab1-1 mutant brain.
Figure 3: Altered positions of mdab1-1 neurons in cerebral cortex.
Figure 4: Reelin is appropriately expressed in mDab1-deficient embryos and mDab1 p80 is expressed in neurons.

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Acknowledgements

We thank F. Gertler and Y. Gotoh for advice; T. Knight, P. Goodwin, C. Auger, E. Gonzales and L. O'Neal for technical assistance; K. Mikoshiba, T. Miyata and K. Nakajima for the CR-50 antibody; and T. Curran and M. Sheldon for discussions. This work was supported by the NIH (J.A.C. and P.S.) and MRC Canada (R.H.).

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  1. Correspondence and requests for materials should be addressed to B.W.H.

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    Correspondence to Brian W. Howell.

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    Howell, B., Hawkes, R., Soriano, P. et al. Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389, 733–737 (1997). https://doi.org/10.1038/39607

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