During the development of the human brain, the layers of the cerebral cortex are formed by

900 WordsApr 23, 20194 Pages
During the development of the human brain, the layers of the cerebral cortex are formed by migrating neurons which come from specialized proliferating regions lying deep in the brain. This neural migration comprises neurons moving as far as one thousand times their own body lengths before they arrive at their destination. During this developmental process, the cortex is divided into six organized layers. In Lissencephaly, this organized cortical layering is disrupted and instead forms four unorganized layers1. It is a severe developmental brain disorder which is characterized by a smooth brain with an abnormal thick cortex, enlarged ventricles, and very few or no gyri2. At the basis of this disease lies failure of proper migration of…show more content…
The C-Terminal Ser/Pro-rich domain has no known function in microtubule binding as of yet. Rather, it functions as an interaction site for other molecules. This suggests that DCX is involved in signaling pathways: DCX is phosphorylated by both Cyclin-dependent kinase 5 (CDK5) and c-jun NH2-terminal kinase (JNK)7,8 at the Ser/Pro-rich domain. Phosphorylation of DCX by CDK5 controls and localizes DCX to fine perinuclear microtubules but not to microtubule bundles in proximal processes. This phosphorylation is developmentally regulated by p35, the major activating subunit for CDK58. At the growth cones, DCX is co-localized with JNK. Phosphorylation of DCX by JNK facilitates neurite outgrowth during differentiation, a process which is important in migration. Additionally, DCX interacts with JNK–interacting protein-1 (JIP-1), a scaffold protein that facilitates its phosphorylation by JNK and furthermore might provide a crosstalk with the reelin pathway7,9. A defective cortical layering phenotype is also observed in individuals with mutations in the REELIN gene. Other phosporylation proteins for DCX are PKA and MARK. Dcx/microtubule interactions are negatively controlled by PKA and MARK at the growth cones.10 Unlike the other two kinases, PKA and and MARK does not phosporylate DCX at the Ser/Pro domain, but at several other sites, with the most important one being S47. The C-terminal region of DCX regulates filamentous actin polymerization in
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