Interaction of reelin signaling and Lis1 in brain development
- 26 October 2003
- journal article
- letter
- Published by Springer Nature in Nature Genetics
- Vol. 35 (3) , 270-276
- https://doi.org/10.1038/ng1257
Abstract
Loss-of-function mutations in RELN (encoding reelin) or PAFAH1B1 (encoding LIS1) cause lissencephaly, a human neuronal migration disorder1. In the mouse, homozygous mutations in Reln result in the reeler phenotype, characterized by ataxia and disrupted cortical layers2. Pafah1b1+/− mice have hippocampal layering defects, whereas homozygous mutants are embryonic lethal3. Reln encodes an extracellular protein that regulates layer formation by interacting with VLDLR and ApoER2 (Lrp8) receptors4,5,6, thereby phosphorylating the Dab1 signaling molecule7,8,9,10. Lis1 associates with microtubules and modulates neuronal migration11. We investigated interactions between the reelin signaling pathway and Lis1 in brain development. Compound mutant mice with disruptions in the Reln pathway and heterozygous Pafah1b1 mutations had a higher incidence of hydrocephalus and enhanced cortical and hippocampal layering defects. Dab1 and Lis1 bound in a reelin-induced phosphorylation-dependent manner. These data indicate genetic and biochemical interaction between the reelin signaling pathway and Lis1.Keywords
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