Cortical Layer Inversion and Deregulation of Reelin Signaling in the Absence of SOCS6 and SOCS7

Mutations of the reelin gene cause severe defects in cerebral cortex development and profound intellectual impairment. While many aspects of the reelin signaling pathway have been identified, the molecular and ultimate cellular consequences of reelin signaling remain unknown. Specifically, it is unc...

Full description

Saved in:
Bibliographic Details
Published inCerebral cortex (New York, N.Y. 1991) Vol. 27; no. 1; pp. 576 - 588
Main Authors Lawrenson, Isobel D, Krebs, Danielle L, Linossi, Edmond M, Zhang, Jian-Guo, McLennan, Tamara J, Collin, Caitlin, McRae, Helen M, Kolesnik, Tatiana B, Koh, Katrina, Britto, Joanne M, Kueh, Andrew J, Sheikh, Bilal N, El-Saafin, Farrah, Nicola, Nicos A, Tan, Seong-Seng, Babon, Jeffrey J, Nicholson, Sandra E, Alexander, Warren S, Thomas, Tim, Voss, Anne K
Format Journal Article
LanguageEnglish
Published United States 01.01.2017
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Mutations of the reelin gene cause severe defects in cerebral cortex development and profound intellectual impairment. While many aspects of the reelin signaling pathway have been identified, the molecular and ultimate cellular consequences of reelin signaling remain unknown. Specifically, it is unclear if termination of reelin signaling is as important for normal cortical neuron migration as activation of reelin signaling. Using mice that are single or double deficient, we discovered that combined loss of the suppressors of cytokine signaling, SOCS6 and SOCS7, recapitulated the cortical layer inversion seen in mice lacking reelin and led to a dramatic increase in the reelin signaling molecule disabled (DAB1) in the cortex. The SRC homology domains of SOCS6 and SOCS7 bound DAB1 ex vivo. Mutation of DAB1 greatly diminished binding and protected from degradation by SOCS6. Phosphorylated DAB1 was elevated in cortical neurons in the absence of SOCS6 and SOCS7. Thus, constitutive activation of reelin signaling was observed to be equally detrimental as lack of activation. We hypothesize that, by terminating reelin signaling, SOCS6 and SOCS7 may allow new cycles of reelin signaling to occur and that these may be essential for cortical neuron migration.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhv253