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Developmental neurobiology

Decoding the Reelin signal

Nature volume 399, pages 645–646 (1999)Cite this article

Back in 1995, the reeler gene was cloned and its protein product was christened Reelin1. Since then, the Reelin signalling pathway — which is involved in brain development — has been progressively unravelled. The latest, most unexpected, twist is now reported in Cell , where Trommsdorff et al .2 show that mice lacking both the very low density lipoprotein (VLDL) receptor and apolipoprotein E receptor-2 (ApoE-R2) genes have the same characteristics as mice that lack Reelin.

Reelin is a large glycoprotein1 found in the extracellular matrix that is secreted by, and surrounds, cells. Reelin is secreted by a variety of neurons, most notably by Cajal-Retzius cells in the cortical marginal zone, and by cerebellar granule cells. But it is not expressed by those neurons that show disrupted patterns (the reeler phenotype), such as cortical-plate neurons or cerebellar Purkinje cells. This suggests that Reelin acts at a distance on target cells, via the extracellular matrix. Two years ago, it was shown that the reeler phenotype can also result from mutations of mouse Disabled-1 (Dab1). This phosphotyrosine protein, which resides in the cytoplasm, is thought to interact with tyrosine kinases of the Src and Abl families4,5,6,. Unlike Reelin, Dab1 is expressed in the neurons that manifest the reeler phenotype, suggesting that it is a key element of the response to a Reelin signal. Indeed, phosphorylation of Dab1 is decreased in Reelin-deficient embryos, but increased when Reelin is added to neuronal cultures7. Until now, the molecules in the cell membrane that sense the presence of Reelin in the extracellular matrix and relay this signal to the cell via Dab1 have been a mystery.

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Figure 1: Lipoprotein receptors and the Reelin signalling pathway.

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  1. Neurobiology Unit, University of Namur Medical School, 61 rue de Bruxelles, B5000, Namur, Belgium

    Isabelle Bar & André M. Goffinet

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  1. Isabelle Bar
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  2. André M. Goffinet
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Bar, I., Goffinet, A. Decoding the Reelin signal . Nature 399, 645–646 (1999). https://doi.org/10.1038/21340

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