Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons.
Bottom Line: Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism.Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation.This finding identifies Cdk5 as a crucial signaling factor in cortical interneuron development in mammals.
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.Show MeSH
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Mentions: Next, we compared interneuron phenotype in the developing Cx of p35 and conditional ErbB4HER4heart KOs by using immunohistochemistry with calbindin (CB) ab. In both KO mice we detected significantly fewer CB+ cells in the Cx compared with control animals (WT: 49 ± 2 vs. p35 KO: 31 ± 1 at E13; ErbB4HER4heart, HET: 92 ± 3 vs. KO: 61 ± 2 at E13.5; Figs 7A–C, E–G and 8M). However, the number of CB+ cells in the striatum at E14.5 was increased in p35- and reduced in ErbB4-lacking animals compared with control littermates (WT: 913 ± 33 vs. p35 KO: 1043 ± 30; ErbB4HER4heart, HET: 951 ± 31 vs. KO: 801 ± 29; Fig. 7D,H). Therefore, in p35 KOs, interneurons failed to cross the PSB and exhibited a “cortical migratory defect,” while in ErbB4 conditional KOs these cells could not advance through the LGE/striatum, thus showing a “GE migratory defect” (see Fig. 5K). Besides, the levels of ErbBs, ligands and associated molecules, assessed in a microarray study, remain normal in embryonic p35 KOs (Supplementary Table 2), as well as cell proliferation and cell death in the embryonic forebrain in both the p35 and ErbB4HER4heart KOs (Supplementary Fig. 5).Figure 7.
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1 6BT, UK.